- Email: [email protected]
Microtubule Modification: Acetylation Speeds Anterograde Traffic Flow
Current Biology Vol 17 No 1 R18
contemporary allele frequencies at the Adh locus along the east coast of Australia. Although the slope of the cline did not change over the 20 year study period, there was a shift equivalent to 4 in latitude in the Adh cline, with the southern high-latitude populations now having the genetic constitution of more northerly populations. Maximum daily temperature measures had increased and both humidity and rainfall had decreased over this period. These findings show the power of latitudinally varying genetic markers to reveal the effects of climate change on natural populations. Widespread generalist species such as D. melanogaster and D. subobscura, which have short generation times and rapidly form phenotypic and genotypic clines, appear to be excellent candidates for sensitive indicators. The marker changes also illustrate the adaptive potential that exists in widespread species with short generation times. But species with long generation times [15], or restricted species with low additive genetic variance for climatic stress traits [16] may show very different patterns and evolutionary potential. Studies of genetic changes in a variety of species should shed light on the variation in rates and magnitudes of evolution in response to climate change in different species. Ongoing work in D. melanogaster and other model organisms is leading to the identification of candidate genes responsible for climatic adaptation. As candidate genes emerge, they offer new prospects for linking climate change to evolutionary shifts in populations. When markers have not been historically characterized in populations, museum specimens may provide samples for longitudinal studies, as demonstrated in the case of insecticide resistance [17]. For now, rapid changes in inversion polymorphisms such as those found in D. subobscura, provide evidence for genetic responses to climate change over broad geographic regions.
References 1. Hansen, J., Sato, M., Ruedy, R., Lo, K., Lea, D.W., and Medina-Elizade, M. (2006). Global temperature change. Proc. Natl. Acad. Sci. USA 103, 14288–14293. 2. Crick, H.Q.P., Dudley, C., Glue, D.E., and Thompson, D.L. (1997). UK birds are laying eggs earlier. Nature 388, 526. 3. Beebee, T.J.C. (1995). Amphibian breeding and climate. Nature 374, 219–220. 4. Parmesan, C., and Yohe, G. (2003). A globally coherent fingerprint of climate change impacts across natural systems. Nature 421, 37–42. 5. Bradshaw, W.E., Zani, P.A., and Holzapfel, C.M. (2004). Adaptation to temperate climates. Evolution 58, 1748–1762. 6. Bradshaw, W.E., and Holzapfel, C.M. (2001). Genetic shift in photoperiodic response correlated with global warming. Proc. Natl. Acad. Sci. USA 98, 14509–14511. 7. Phillips, B.L., Brown, G.P., Webb, J.K., and Shine, R. (2006). Invasion and the evolution of speed in toads. Nature 439, 803. 8. Balanya´, J., Oller, J.M., Huey, R.B., Gilchrist, G.W., and Serra, L. (2006). Global genetic change tracks climate warming in Drosophila subobscura. Science 313, 1773–1775. 9. Balanya´, J., Sole´, E., Oller, J.M., Sperlich, D., and Serra, L. (2004). Long-term changes in the chromosomal inversion polymorphism of Drosophila subobscura. II. European populations. J. Zool. Syst. Evol. Res. 42, 191–201. 10. Rodriguez-Trelles, F., and Rodriguez, M.A. (1998). Rapid microevolution and loss of chromosomal diversity in Drosophila in response to climate warming. Evol. Ecol. 12, 829–838. 11. Umina, P.A., Weeks, A.R., Kearney, M.R., McKecknie, S.W., and Hoffmann, A.A.
12.
13.
14.
15.
16.
17.
(2005). A rapid shift in a classic clinal pattern in Drosophila reflecting climate change. Science 308, 691–693. Levitan, M., and Etges, W.J. (2005). Climate change and recent genetic flux in populations of Drosophila robusta. BMC Evol. Biol. 5, 4. Kennington, W.J., Partridge, L., and Hoffmann, A.A. (2006). Patterns of diversity and linkage disequilibrium within the cosmopolitan inversion In(3R)Payne in Drosophila melanogaster are indicative of coadaptation. Genetics 172, 1655–1663. Kirkpatrick, M., and Barton, N. (2006). Chromosome inversions, local adaptation and speciation. Genetics 173, 419–434. Janzen, F.J. (1994). Climate change and temperature-dependent sex determination in reptiles. Proc. Natl. Acad. Sci. USA 91, 7487–7490. Kellermann, V.M., van Heerwaarden, B., Hoffmann, A.A., and Sgro, C.M. (2006). Very low additive genetic variance and evolutionary potential in multiple populations of two rainforest Drosophila species. Evolution 60, 1104–1108. Hartley, C.J., Newcomb, R.D., Russell, R.J., Yong, C.G., Stevens, J.R., Yeates, D.K., La Salle, J., and Oakeshott, J.G. (2006). Amplification of DNA from preserved specimens shows blowflies were preadapted for the rapid evolution of insecticide resistance. Proc. Natl. Acad. Sci. USA 103, 8757–8762.
Centre for Environmental Stress and Adaptation Research, Department of Genetics, The University of Melbourne, Victoria 3010, Australia. E-mail: [email protected]
DOI: 10.1016/j.cub.2006.11.035
Microtubule Modification: Acetylation Speeds Anterograde Traffic Flow Microtubules in neurites undergo multiple post-translational modifications. Recent work shows that neurites enriched in acetylated microtubules selectively support kinesin-mediated transport of the JNK regulator JIP-1 to growth cones. J. Chloe¨ Bulinski Back in the 1970s, a subset of tubulin molecules in the vertebrate brain was shown to undergo an enzyme-mediated, RNA-independent incorporation of tyrosine into the carboxyl terminus of its a-subunit [1]. Ever since this observation, researchers have speculated on how this so-called tyrosination/detyrosination modification — as well as other, subsequently discovered but equally intriguing,
post-translational modifications such as acetylation [2], and polyglutamylation [3] — could affect the function of the microtubule polymers in which the modified tubulin subunits are found [4]. Like tyrosination/detyrosination [5], acetylation and poly-glutamylation were shown to be reversible, with the primary modification occurring on the microtubules, such that modified tubulin subunits accumulate in more stable, i.e., long-lived, populations of microtubules [6] that are localized
Dispatch R19
to a subset of neuritic processes [7,8]. Although the chemically modified subunits were proposed to act as markers of the stability or orientation of the modified microtubules, with microtubule motors or other microtubuleassociated proteins competent to interpret these signals [8], it is safe to say that only glimpses of insight into the possible functions of tubulin post-translational modifications have emerged since their discovery. That is, until now: a paper from Verhey and colleagues [9] published in a recent issue of Current Biology provides strong evidence from studies of a CNS cell line and primary hippocampal neurons to show that acetylated microtubules serve as ‘high occupancy vesicle’ (HOV) lanes for kinesin-mediated delivery of JIP-1-containing vesicles to the tips of neurites. Since the original identification in yeast two-hybrid experiments of c-Jun N-terminal kinase (JNK)-interacting proteins (JIP-1 through JIP-4) as cargoes for anterograde transport by kinesin [10], their importance has been established in activating JNK [11] and regulating the JNK-mediated phosphorylation of several growth-cone-resident substrates, notably the microtubule-binding protein doublecortin [12]. Indeed, although JIP-1 was originally localized to axonal and dendritic growth cones [13], its role in blocking apoptosis, possibly by signaling that neurites have achieved appropriate stability or forged the correct distal contacts [14], has argued that cells must not only use kinesin to move JIP-1 to the tips of neurites, but also must have a means of selectively transporting JIP-1 down particular neurites. Given that the subset of microtubules that is enriched in detyrosinated tubulin appears to be altered in the transport of kinesin-dependent cargo [15–17], Verhey and colleagues [9] tested the hypothesis that the post-translational modifications that chemically alter microtubules in neuronal processes can help to modulate the anterograde traffic flow down individual neurites. A combination of results from novel
Acetylated MTs
Unmodified MTs
Detyrosinated MTs
JIP-1
Poly-glutamylated MTs Current Biology
Figure 1. Microtubules (MTs) in neurons undergo multiple reversible post-translational modifications. Only those microtubules that are acetylated support kinesin transport of JIP-1 to their tips. Although microtubules in the same process actually carry multiple modifications (and are only shown in the figure to have one type of modification per process for simplicity’s sake), the work from Verhey and colleagues [9] shows that it is their acetylation that is sufficient to increase the transport (denoted by the bold arrows), while the other post-translational modifications — detyrosination and poly-glutamylation — appear to make a smaller impact on transport (denoted by the light arrows).
and more standard experiments performed with the CNS cell line, CAD [18], hippocampal neurons and genetically engineered microtubules from Tetrahymena provides strong support for the hypothesis by showing that heightened post-translational acetylation of the microtubules in a neurite is sufficient to direct kinesin-mediated transport of vesicles to its tip (Figure 1). This paper first reveals that the population of JIP-1 that is localized to a subset of neurite tips is dynamic, because it recovers fluorescence rapidly after photobleaching and loses fluorescence rapidly after photo-activation, indicating that selective kinesin-mediated transport of JIP-1 to particular neurite tips reflects a continued selective use of particular microtubule tracks. The authors then demonstrate that, although other post-translational
modifications, such as poly-glutamylation of a- or b-tubulin, also occur in these neurites and detyrosination of atubulin may contribute to selective transport via higher affinity kinesin binding, JIP-1 localization correlates better with microtubule acetylation state. Accordingly, Verhey and colleagues [9] then utilize preparations of axonemes and singlet microtubules from genetically manipulated clones of the holotrichous ciliate Tetrahymena to show that acetylation of a-tubulin enhances kinesin motility. Putting these results together, they show that hyper-acetylation of all microtubules in the CAD or hippocampal neurons is sufficient to target JIP-1 to all neurite tips, thus abrogating the normal selectivity of its transport. Thus, in contrast to the volumes of data that have been amassed on the proposed function(s) of the
Current Biology Vol 17 No 1 R20
intriguing post-translational modifications of tubulin, this is the first paper that has convincingly delineated the contribution of one modification — acetylation of a-tubulin — to the spatial selectivity in the transport of a particular signaling molecule in an asymmetric cell. References 1. Arce, C.A., Rodriguez, J.A., Barra, H.S., and Caputo, R. (1975). Incorporation of L-tyrosine, L-phenylalanine and L-3,4dihydroxyphenylalanine as single units into rat brain tubulin. Eur. J. Biochem. 59, 145–149. 2. L’Hernault, S.W., and Rosenbaum, J.L. (1985). Chlamydomonas alpha-tubulin is posttranslationally modified by acetylation on the epsilon-amino group of a lysine. Biochemistry 24, 473–478. 3. Edde, B., Rossier, J., Le Caer, J.P., Desbruyeres, E., Gros, F., and Denoulet, P. (1990). Posttranslational glutamylation of alpha-tubulin. Science 247, 83–85. 4. Westermann, S., and Weber, K. (2003). Post-translational modifications regulate microtubule function. Nat. Rev. Mol. Cell Biol. 4, 938–947. 5. Argarana, C.E., Barra, H.S., and Caputto, R. (1978). Release of [14C]tyrosine from tubulinyl-[14C]tyrosine by brain extract. Separation of a carboxypeptidase from tubulin-tyrosine ligase. Mol. Cell Biochem. 19, 17–21. 6. Gundersen, G.G., Khawaja, S., and Bulinski, J.C. (1987). Postpolymerization
7.
8.
9.
10.
11.
12.
13.
detyrosination of alpha-tubulin: a mechanism for subcellular differentiation of microtubules. J. Cell Biol. 105, 251–264. Wehland, J., and Weber, K. (1987). Turnover of the carboxy-terminal tyrosine of alpha-tubulin and means of reaching elevated levels of detyrosination in living cells. J. Cell Sci. 88, 185–203. Bulinski, J.C., and Gundersen, G.G. (1991). Stabilization of post-translational modification of microtubules during cellular morphogenesis. Bioessays 13, 285–293. Reed, N.A., Cai, D., Blasius, T.L., Jih, G.T., Meyhofer, E., Gaertig, J., and Verhey, K. (2006). Microtubule acetylation promotes kinesin-1 binding and transport. Curr. Biol. 16, 2166–2172. Verhey, K.J., Meyer, D., Deehan, R., Blenis, J., Schnapp, B.J., Rapoport, T.A., and Margolis, B. (2001). Cargo of kinesin identified as JIP scaffolding proteins and associated signaling molecules. J. Cell Biol. 152, 959–970. Levresse, V., Butterfield, L., Zentrich, E., and Heasley, L.E. (2000). Akt negatively regulates the cJun N-terminal kinase pathway in PC12 cells. J. Neurosci. Res. 62, 799–808. Gdalyahu, A., Ghosh, I., Levy, T., Sapir, T., Sapoznik, S., Fishler, Y., Azoulai, D., and Reiner, O. (2004). DCX, a new mediator of the JNK pathway. EMBO J. 23, 823–832. Pellet, J.B., Haefliger, J.A., Staple, J.K., Widmann, C., Welker, E., Hirling, H., Bonny, C., Nicod, P., Catsicas, S., Waeber, G., et al. (2000). Spatial, temporal and subcellular localization of islet-brain 1 (IB1), a homologue of JIP-1, in mouse brain. Eur. J. Neurosci. 12, 621–632.
Visual Neuroscience: Face-Encoding Mechanisms Revealed by Adaptation Faces convey a great variety of information, for example about the species, gender, age, identity and even mood or intentions. A recent study sheds light on the neural mechanisms for encoding a face’s gaze direction. Rodrigo Sigala and Gregor Rainer How does the brain deal with all the complex signals that pour in from the body’s sense organs quickly and accurately? How do we manage to extract the relevant information present in every face? The answers to these and other questions seem to be part of an old and more general question: does the brain solve complex tasks like face recognition through a variety of specialized ‘modules’, or through ‘distributed’ processing of information? The first hypothesis assumes that face processing is
carried out by neurons with similar characteristics located in welldefined, small areas of the brain. The second hypothesis suggests that faces are encoded by large populations of neurons distributed across wide cortical regions. Experiments comparing the recognition of faces to that of other objects in brain-damaged or healthy subjects have identified some characteristics that are special to the processing of face stimuli [1]. At the same time, neuroimaging studies identified three basic areas that respond more strongly to face images than
14. Harding, T.C., Xue, L., Bienemann, A., Haywood, D., Dickens, M., Tolkovsky, A.M., and Uney, J.B. (2001). Inhibition of JNK by overexpression of the JNL binding domain of JIP-1 prevents apoptosis in sympathetic neurons. J. Biol. Chem. 276, 4531–4534. 15. Kreitzer, G., Liao, G., and Gundersen, G.G. (1999). Detyrosination of tubulin regulates the interaction of intermediate filaments with microtubules in vivo via a kinesindependent mechanism. Mol. Biol. Cell 10, 1105–1118. 16. Liao, G., and Gundersen, G.G. (1998). Kinesin is a candidate for cross-bridging microtubules and intermediate filaments. Selective binding of kinesin to detyrosinated tubulin and vimentin. J. Biol. Chem. 273, 9797–9803. 17. Lin, S.X., Gundersen, G.G., and Maxfield, F.R. (2002). Export from pericentriolar endocytic recycling compartment to cell surface depends on stable, detyrosinated (glu) microtubules and kinesin. Mol. Biol. Cell 13, 96–109. 18. Qi, Y., Wang, J.K., McMillian, M., and Chikaraishi, D.M. (1997). Characterization of a CNS cell line, CAD, in which morphological differentiation is initiated by serum deprivation. J. Neurosci. 17, 1217–1225.
Biological Sciences and Pathology & Cell Biology, Columbia University, 804A Sherman Fairchild Center, MC 2450, 1212 Amsterdam Avenue, New York, New York 10027-2450, USA. E-mail: [email protected] DOI: 10.1016/j.cub.2006.11.036
to other objects tested: the fusiform gyrus, the inferior occipital gyrus and the superior temporal sulcus [2]. Together with this evidence, electrophysiological recordings in the inferior temporal monkey cortex showed that face stimuli elicited in some neurons, dubbed ‘face-cells’, significantly higher responses compared to any other visual stimuli tested (see [3] for a review). A recent study [4] that combined functional magnetic resonance imaging (fMRI) and electrophysiological recordings on the monkey brain described patches of cortex containing 97% of cells with a clearly selective response to faces. If specialized brain areas underlie the representation of behavioral important tasks, like face recognition, the next question to be posed is whether cognitive functions are represented again by specialized submodules, such as ones coding for different aspects of face information. Experiments in humans and monkeys have already
contemporary allele frequencies at the Adh locus along the east coast of Australia. Although the slope of the cline did not change over the 20 year study period, there was a shift equivalent to 4 in latitude in the Adh cline, with the southern high-latitude populations now having the genetic constitution of more northerly populations. Maximum daily temperature measures had increased and both humidity and rainfall had decreased over this period. These findings show the power of latitudinally varying genetic markers to reveal the effects of climate change on natural populations. Widespread generalist species such as D. melanogaster and D. subobscura, which have short generation times and rapidly form phenotypic and genotypic clines, appear to be excellent candidates for sensitive indicators. The marker changes also illustrate the adaptive potential that exists in widespread species with short generation times. But species with long generation times [15], or restricted species with low additive genetic variance for climatic stress traits [16] may show very different patterns and evolutionary potential. Studies of genetic changes in a variety of species should shed light on the variation in rates and magnitudes of evolution in response to climate change in different species. Ongoing work in D. melanogaster and other model organisms is leading to the identification of candidate genes responsible for climatic adaptation. As candidate genes emerge, they offer new prospects for linking climate change to evolutionary shifts in populations. When markers have not been historically characterized in populations, museum specimens may provide samples for longitudinal studies, as demonstrated in the case of insecticide resistance [17]. For now, rapid changes in inversion polymorphisms such as those found in D. subobscura, provide evidence for genetic responses to climate change over broad geographic regions.
References 1. Hansen, J., Sato, M., Ruedy, R., Lo, K., Lea, D.W., and Medina-Elizade, M. (2006). Global temperature change. Proc. Natl. Acad. Sci. USA 103, 14288–14293. 2. Crick, H.Q.P., Dudley, C., Glue, D.E., and Thompson, D.L. (1997). UK birds are laying eggs earlier. Nature 388, 526. 3. Beebee, T.J.C. (1995). Amphibian breeding and climate. Nature 374, 219–220. 4. Parmesan, C., and Yohe, G. (2003). A globally coherent fingerprint of climate change impacts across natural systems. Nature 421, 37–42. 5. Bradshaw, W.E., Zani, P.A., and Holzapfel, C.M. (2004). Adaptation to temperate climates. Evolution 58, 1748–1762. 6. Bradshaw, W.E., and Holzapfel, C.M. (2001). Genetic shift in photoperiodic response correlated with global warming. Proc. Natl. Acad. Sci. USA 98, 14509–14511. 7. Phillips, B.L., Brown, G.P., Webb, J.K., and Shine, R. (2006). Invasion and the evolution of speed in toads. Nature 439, 803. 8. Balanya´, J., Oller, J.M., Huey, R.B., Gilchrist, G.W., and Serra, L. (2006). Global genetic change tracks climate warming in Drosophila subobscura. Science 313, 1773–1775. 9. Balanya´, J., Sole´, E., Oller, J.M., Sperlich, D., and Serra, L. (2004). Long-term changes in the chromosomal inversion polymorphism of Drosophila subobscura. II. European populations. J. Zool. Syst. Evol. Res. 42, 191–201. 10. Rodriguez-Trelles, F., and Rodriguez, M.A. (1998). Rapid microevolution and loss of chromosomal diversity in Drosophila in response to climate warming. Evol. Ecol. 12, 829–838. 11. Umina, P.A., Weeks, A.R., Kearney, M.R., McKecknie, S.W., and Hoffmann, A.A.
12.
13.
14.
15.
16.
17.
(2005). A rapid shift in a classic clinal pattern in Drosophila reflecting climate change. Science 308, 691–693. Levitan, M., and Etges, W.J. (2005). Climate change and recent genetic flux in populations of Drosophila robusta. BMC Evol. Biol. 5, 4. Kennington, W.J., Partridge, L., and Hoffmann, A.A. (2006). Patterns of diversity and linkage disequilibrium within the cosmopolitan inversion In(3R)Payne in Drosophila melanogaster are indicative of coadaptation. Genetics 172, 1655–1663. Kirkpatrick, M., and Barton, N. (2006). Chromosome inversions, local adaptation and speciation. Genetics 173, 419–434. Janzen, F.J. (1994). Climate change and temperature-dependent sex determination in reptiles. Proc. Natl. Acad. Sci. USA 91, 7487–7490. Kellermann, V.M., van Heerwaarden, B., Hoffmann, A.A., and Sgro, C.M. (2006). Very low additive genetic variance and evolutionary potential in multiple populations of two rainforest Drosophila species. Evolution 60, 1104–1108. Hartley, C.J., Newcomb, R.D., Russell, R.J., Yong, C.G., Stevens, J.R., Yeates, D.K., La Salle, J., and Oakeshott, J.G. (2006). Amplification of DNA from preserved specimens shows blowflies were preadapted for the rapid evolution of insecticide resistance. Proc. Natl. Acad. Sci. USA 103, 8757–8762.
Centre for Environmental Stress and Adaptation Research, Department of Genetics, The University of Melbourne, Victoria 3010, Australia. E-mail: [email protected]
DOI: 10.1016/j.cub.2006.11.035
Microtubule Modification: Acetylation Speeds Anterograde Traffic Flow Microtubules in neurites undergo multiple post-translational modifications. Recent work shows that neurites enriched in acetylated microtubules selectively support kinesin-mediated transport of the JNK regulator JIP-1 to growth cones. J. Chloe¨ Bulinski Back in the 1970s, a subset of tubulin molecules in the vertebrate brain was shown to undergo an enzyme-mediated, RNA-independent incorporation of tyrosine into the carboxyl terminus of its a-subunit [1]. Ever since this observation, researchers have speculated on how this so-called tyrosination/detyrosination modification — as well as other, subsequently discovered but equally intriguing,
post-translational modifications such as acetylation [2], and polyglutamylation [3] — could affect the function of the microtubule polymers in which the modified tubulin subunits are found [4]. Like tyrosination/detyrosination [5], acetylation and poly-glutamylation were shown to be reversible, with the primary modification occurring on the microtubules, such that modified tubulin subunits accumulate in more stable, i.e., long-lived, populations of microtubules [6] that are localized
Dispatch R19
to a subset of neuritic processes [7,8]. Although the chemically modified subunits were proposed to act as markers of the stability or orientation of the modified microtubules, with microtubule motors or other microtubuleassociated proteins competent to interpret these signals [8], it is safe to say that only glimpses of insight into the possible functions of tubulin post-translational modifications have emerged since their discovery. That is, until now: a paper from Verhey and colleagues [9] published in a recent issue of Current Biology provides strong evidence from studies of a CNS cell line and primary hippocampal neurons to show that acetylated microtubules serve as ‘high occupancy vesicle’ (HOV) lanes for kinesin-mediated delivery of JIP-1-containing vesicles to the tips of neurites. Since the original identification in yeast two-hybrid experiments of c-Jun N-terminal kinase (JNK)-interacting proteins (JIP-1 through JIP-4) as cargoes for anterograde transport by kinesin [10], their importance has been established in activating JNK [11] and regulating the JNK-mediated phosphorylation of several growth-cone-resident substrates, notably the microtubule-binding protein doublecortin [12]. Indeed, although JIP-1 was originally localized to axonal and dendritic growth cones [13], its role in blocking apoptosis, possibly by signaling that neurites have achieved appropriate stability or forged the correct distal contacts [14], has argued that cells must not only use kinesin to move JIP-1 to the tips of neurites, but also must have a means of selectively transporting JIP-1 down particular neurites. Given that the subset of microtubules that is enriched in detyrosinated tubulin appears to be altered in the transport of kinesin-dependent cargo [15–17], Verhey and colleagues [9] tested the hypothesis that the post-translational modifications that chemically alter microtubules in neuronal processes can help to modulate the anterograde traffic flow down individual neurites. A combination of results from novel
Acetylated MTs
Unmodified MTs
Detyrosinated MTs
JIP-1
Poly-glutamylated MTs Current Biology
Figure 1. Microtubules (MTs) in neurons undergo multiple reversible post-translational modifications. Only those microtubules that are acetylated support kinesin transport of JIP-1 to their tips. Although microtubules in the same process actually carry multiple modifications (and are only shown in the figure to have one type of modification per process for simplicity’s sake), the work from Verhey and colleagues [9] shows that it is their acetylation that is sufficient to increase the transport (denoted by the bold arrows), while the other post-translational modifications — detyrosination and poly-glutamylation — appear to make a smaller impact on transport (denoted by the light arrows).
and more standard experiments performed with the CNS cell line, CAD [18], hippocampal neurons and genetically engineered microtubules from Tetrahymena provides strong support for the hypothesis by showing that heightened post-translational acetylation of the microtubules in a neurite is sufficient to direct kinesin-mediated transport of vesicles to its tip (Figure 1). This paper first reveals that the population of JIP-1 that is localized to a subset of neurite tips is dynamic, because it recovers fluorescence rapidly after photobleaching and loses fluorescence rapidly after photo-activation, indicating that selective kinesin-mediated transport of JIP-1 to particular neurite tips reflects a continued selective use of particular microtubule tracks. The authors then demonstrate that, although other post-translational
modifications, such as poly-glutamylation of a- or b-tubulin, also occur in these neurites and detyrosination of atubulin may contribute to selective transport via higher affinity kinesin binding, JIP-1 localization correlates better with microtubule acetylation state. Accordingly, Verhey and colleagues [9] then utilize preparations of axonemes and singlet microtubules from genetically manipulated clones of the holotrichous ciliate Tetrahymena to show that acetylation of a-tubulin enhances kinesin motility. Putting these results together, they show that hyper-acetylation of all microtubules in the CAD or hippocampal neurons is sufficient to target JIP-1 to all neurite tips, thus abrogating the normal selectivity of its transport. Thus, in contrast to the volumes of data that have been amassed on the proposed function(s) of the
Current Biology Vol 17 No 1 R20
intriguing post-translational modifications of tubulin, this is the first paper that has convincingly delineated the contribution of one modification — acetylation of a-tubulin — to the spatial selectivity in the transport of a particular signaling molecule in an asymmetric cell. References 1. Arce, C.A., Rodriguez, J.A., Barra, H.S., and Caputo, R. (1975). Incorporation of L-tyrosine, L-phenylalanine and L-3,4dihydroxyphenylalanine as single units into rat brain tubulin. Eur. J. Biochem. 59, 145–149. 2. L’Hernault, S.W., and Rosenbaum, J.L. (1985). Chlamydomonas alpha-tubulin is posttranslationally modified by acetylation on the epsilon-amino group of a lysine. Biochemistry 24, 473–478. 3. Edde, B., Rossier, J., Le Caer, J.P., Desbruyeres, E., Gros, F., and Denoulet, P. (1990). Posttranslational glutamylation of alpha-tubulin. Science 247, 83–85. 4. Westermann, S., and Weber, K. (2003). Post-translational modifications regulate microtubule function. Nat. Rev. Mol. Cell Biol. 4, 938–947. 5. Argarana, C.E., Barra, H.S., and Caputto, R. (1978). Release of [14C]tyrosine from tubulinyl-[14C]tyrosine by brain extract. Separation of a carboxypeptidase from tubulin-tyrosine ligase. Mol. Cell Biochem. 19, 17–21. 6. Gundersen, G.G., Khawaja, S., and Bulinski, J.C. (1987). Postpolymerization
7.
8.
9.
10.
11.
12.
13.
detyrosination of alpha-tubulin: a mechanism for subcellular differentiation of microtubules. J. Cell Biol. 105, 251–264. Wehland, J., and Weber, K. (1987). Turnover of the carboxy-terminal tyrosine of alpha-tubulin and means of reaching elevated levels of detyrosination in living cells. J. Cell Sci. 88, 185–203. Bulinski, J.C., and Gundersen, G.G. (1991). Stabilization of post-translational modification of microtubules during cellular morphogenesis. Bioessays 13, 285–293. Reed, N.A., Cai, D., Blasius, T.L., Jih, G.T., Meyhofer, E., Gaertig, J., and Verhey, K. (2006). Microtubule acetylation promotes kinesin-1 binding and transport. Curr. Biol. 16, 2166–2172. Verhey, K.J., Meyer, D., Deehan, R., Blenis, J., Schnapp, B.J., Rapoport, T.A., and Margolis, B. (2001). Cargo of kinesin identified as JIP scaffolding proteins and associated signaling molecules. J. Cell Biol. 152, 959–970. Levresse, V., Butterfield, L., Zentrich, E., and Heasley, L.E. (2000). Akt negatively regulates the cJun N-terminal kinase pathway in PC12 cells. J. Neurosci. Res. 62, 799–808. Gdalyahu, A., Ghosh, I., Levy, T., Sapir, T., Sapoznik, S., Fishler, Y., Azoulai, D., and Reiner, O. (2004). DCX, a new mediator of the JNK pathway. EMBO J. 23, 823–832. Pellet, J.B., Haefliger, J.A., Staple, J.K., Widmann, C., Welker, E., Hirling, H., Bonny, C., Nicod, P., Catsicas, S., Waeber, G., et al. (2000). Spatial, temporal and subcellular localization of islet-brain 1 (IB1), a homologue of JIP-1, in mouse brain. Eur. J. Neurosci. 12, 621–632.
Visual Neuroscience: Face-Encoding Mechanisms Revealed by Adaptation Faces convey a great variety of information, for example about the species, gender, age, identity and even mood or intentions. A recent study sheds light on the neural mechanisms for encoding a face’s gaze direction. Rodrigo Sigala and Gregor Rainer How does the brain deal with all the complex signals that pour in from the body’s sense organs quickly and accurately? How do we manage to extract the relevant information present in every face? The answers to these and other questions seem to be part of an old and more general question: does the brain solve complex tasks like face recognition through a variety of specialized ‘modules’, or through ‘distributed’ processing of information? The first hypothesis assumes that face processing is
carried out by neurons with similar characteristics located in welldefined, small areas of the brain. The second hypothesis suggests that faces are encoded by large populations of neurons distributed across wide cortical regions. Experiments comparing the recognition of faces to that of other objects in brain-damaged or healthy subjects have identified some characteristics that are special to the processing of face stimuli [1]. At the same time, neuroimaging studies identified three basic areas that respond more strongly to face images than
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Biological Sciences and Pathology & Cell Biology, Columbia University, 804A Sherman Fairchild Center, MC 2450, 1212 Amsterdam Avenue, New York, New York 10027-2450, USA. E-mail: [email protected] DOI: 10.1016/j.cub.2006.11.036
to other objects tested: the fusiform gyrus, the inferior occipital gyrus and the superior temporal sulcus [2]. Together with this evidence, electrophysiological recordings in the inferior temporal monkey cortex showed that face stimuli elicited in some neurons, dubbed ‘face-cells’, significantly higher responses compared to any other visual stimuli tested (see [3] for a review). A recent study [4] that combined functional magnetic resonance imaging (fMRI) and electrophysiological recordings on the monkey brain described patches of cortex containing 97% of cells with a clearly selective response to faces. If specialized brain areas underlie the representation of behavioral important tasks, like face recognition, the next question to be posed is whether cognitive functions are represented again by specialized submodules, such as ones coding for different aspects of face information. Experiments in humans and monkeys have already