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Membrane Traffic: Arl GTPases Get a GRIP on the Golgi
Current Biology, Vol. 13, R174–R176, March 4, 2003, ©2003 Elsevier Science Ltd. All rights reserved.
Membrane Traffic: Arl GTPases Get a GRIP on the Golgi Catherine L. Jackson
A subset of the golgin family of large coiled-coil proteins have a GRIP domain that mediates their localization to the trans-Golgi. Two recent papers show that the Arl3p and Arl1p small GTPases act sequentially to recruit GRIP domain proteins to the Golgi.
The Golgi apparatus is the central sorting organelle in eukaryotic cells, situated at the intersection of exocytic and endocytic membrane trafficking pathways. Membrane fusion is essential for protein transport through the Golgi, and takes place in several discrete steps that ensure specificity of the final fusion event. The first step is known as tethering, and a number of proteins have been implicated in this process, including the golgins [1]. These large Golgi-localized proteins have an extended coiled-coil conformation, and play an important role in maintaining Golgi structure in all eukaryotic cells from yeast to humans. Previous work showed that a subset of the golgins contain a carboxyterminal region, called the GRIP domain, that mediates binding to Golgi membranes [2–4]. Two papers in this issue of Current Biology have now demonstrated the mechanism by which GRIP domains are recruited to the Golgi [5,6]. These papers show that the small GTPases Arl3p and Arl1p, in their GTP-bound active conformations, act sequentially to recruit GRIP domain proteins to the Golgi in yeast. The Arl proteins themselves had been shown previously to play important roles in trafficking through the Golgi, but the molecular details were not known [7–10]. These results are an important step towards elucidating the molecular mechanisms coordinating Golgi structure with trafficking through this complex organelle. Arl (for ADP-ribosylation factor-like) GTP-binding proteins are a subfamily of the ADP-ribosylation factor (Arf) branch of the small G protein superfamily. The Arl proteins are highly conserved through evolution, and have diverse functions including regulation of membrane trafficking [11]. The yeast Saccharomyces cerevisiae has two Arl proteins, Arl1p and Arl3p, both of which appear to play roles in trafficking in the transGolgi network (TGN)-endosomal system [7,9]. The mammalian homologues of Arl1p and Arl3p are ARL1 and Arf-related protein (ARFRP1), respectively. ARL1 is involved in the regulation of Golgi structure, is localized to the TGN in mammalian cells, and regulates trafficking in the TGN-endosomal system like its yeast counterpart [8,10]. Deletion of ARFRP1 in mice leads to early embryonic lethality and a mutation in Drosophila Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA. E-mail: [email protected]
PII S0960-9822(03)00116-7
Dispatch
ARL1 is zygotic lethal, indicating essential roles for both of these proteins in metazoans [12,13]. The golgins also play an important role in the structure and functioning of the Golgi apparatus in eukaryotic organisms. These proteins were originally identified as the antigens recognized by autoantibodies present in the serum of patients with autoimmune disorders such as Sjögren’s syndrome [14]. Aside from short amino- and carboxy-terminal domains, the golgins are predicted to adopt an extensive coiledcoil conformation (Figure 1A). At least four golgins (p230/golgin-245, golgin-97, GCC88 and GCC185) in mammalian cells, and one (Imh1p) in S. cerevisiae have at their carboxyl terminus a conserved region called the ‘GRIP’ domain, a ~45 amino acid motif necessary and sufficient for localization of these proteins to Golgi membranes, specifically the TGN [2–4,15]. The four mammalian GRIP-domain golgins each show the same response to treatment by the drug brefeldin A (BFA) in that none of these proteins is rapidly released from Golgi membranes (that is, within 2 minutes of treatment). The golgins are only released after approximately 15 minutes of treatment with the drug, the time at which the Golgi disassembles [15]. Hence the membrane association of the golgins depends on an intact Golgi structure, but is not regulated directly by the Arf proteins, which are direct targets of BFA. The new work published in this issue of Current Biology by Panic et al. [5] and Gangi Setty et al. [6] shows that both Arl1p and Arl3p are required for localization of GRIP-domain proteins to Golgi membranes. Arl1p–GTP interacts specifically with the GRIP domain to recruit it to membranes, and Arl3p is required for normal Golgi localization of Arl1p. Gangi Setty et al. [6] show that it is the activated form of Arl3p, Arl3p–GTP, that is required for Arl1p recruitment to Golgi membranes. The GTPase cycle of Arl3p therefore regulates membrane binding of Arl1p, which in turn, through its own GTPase cycle, regulates Golgi localization of the GRIP-domain proteins. Although the results have so far only been demonstrated in yeast, it is likely that these results will hold true for the mammalian homologues, given the conservation of these proteins at both the sequence and functional levels. Indeed, Gangi Setty et al. [6] show that the GRIP domains of human golgin-97 and mouse tGolgin-1 (the mouse homologue of golgin-245) are recruited to the yeast Golgi by Arl1p–GTP in an Arl3p-dependent manner. In addition, previous work demonstrated a two-hybrid interaction between human ARL1-Q71L (the GTPlocked form) and the GRIP domain of human Golgin245, and co-localization of these two proteins in mammalian cells [10]. The golgins have been proposed to act as tethering factors — proteins or protein complexes that act to hold two fusing membranes in place prior to the actual fusion event [16]. There are now a number of protein complexes that appear to be involved in tethering at
Current Biology R175
Figure 1. Arl3p and Arl1p act sequentially to recruit GRIP-domain proteins to the Golgi. (A) Schematic diagram of GRIP domain proteins. p230/golgin-245, golgin-97, GCC88 and GCC185 are mammalian proteins, and Imh1p is the sole GRIP-domain protein in S. cerevisiae. N, amino-terminal region with no coiled-coil propensity; coiled-coil, large central region predicted to adopt a largely coiled-coil conformation; GRIP, GRIP domain. (B) The Arl3p and Arl1p GTPases act sequentially to recruit GRIP domain proteins to Golgi membranes. Both Arl3p–GDP and Arl1p–GDP are localized to the cytoplasm. Upon nucleotide exchange by as yet unidentified GEFs, each is localized to membranes. Arl3p–GTP could recruit Arl1p directly, through interaction with its GEF, or through interaction with another Arl3p effector. Arl1p–GTP then binds to GRIP-domain proteins, recruiting them to the Golgi membrane.
N
A
Coiled-coil
GRIP
Golgin-97 Golgin-245 GCC88 GCC185 Imh1p B
different sites within cells, including the GARP/VFT complex [1]. GARP/VFT (also known as the Vps52-5354 complex) has been implicated in retrograde transport from endosomal compartments back to the TGN in yeast [17]. Panic et al. [5] show that GARP/VFT binds to Arl1p in its GTP-bound form. Previous work had implicated the Rab protein Ypt6p in membrane localization of the GARP/VFT complex in yeast [18], and it may be that the Ypt6p and Arl1p GTPases together coordinate binding of this complex to membranes. However, unlike the case for the GRIP-domain proteins, GARP/VFT localization is not abrogated in an arl1∆ mutant, indicating either that the Arl1p–GARP interaction serves a different role, or that redundant pathways lead to membrane binding of the GARP/VFT complex. One way to test whether Ypt6p and Arl1p act in separate pathways to recruit GARP/VFT to membranes is to assay localization of the complex in a strain deleted for both Ypt6 and Arl1p. Interestingly, both Panic et al. [5] and Gangi Setty et al. [6] have found that such a strain is inviable, so although the simple experiment cannot be done, this result nevertheless shows that Ypt6 and Arl1p have an essential overlapping function. An attractive hypothesis suggested by the results of Panic et al. [5] is that Arl1p–GTP may recruit multiple tethering factors to membranes, perhaps to distinct locations. Future work will no doubt be directed at testing these ideas. Recently, small GTPases of the Rab family have been shown to act in signaling cascades in which an upstream Rab regulates the function of a Rab protein acting downstream in the secretory pathway [19,20]. Ypt32p localizes to the late Golgi at regions of polarized growth in yeast, and binds directly in its GTPbound form to Sec2p, a guanine nucleotide exchange factor (GEF) for the Sec4p Rab GTPase. Ypt32–GTP thus recruits Sec2p to membranes where it activates Sec4p [19]. It is tempting to speculate that a similar mechanism may hold true for Arl3p and Arl1p (Figure 1B). Since the GEFs for these GTPases are not known, testing this hypothesis will await the identification of
trans-Golgi
Arl3–GTP GEF Arl3–GDP
Arl1–GTP ?
GRIP domain protein
GEF Arl1–GDP Current Biology
Arl3p and Arl1p exchange factors. Other possibilities are that Arl1p interacts directly with Arl3p–GTP, or that Arl1p interacts with another effector of Arl3p (Figure 1B). Determining the molecular details of the Arl3p–Arl1p GTPase cascade, and the regulation of the recruitment of GRIP-domain proteins and potentially other tethering factors to membranes will be fertile ground for future experiments. References 1. Whyte, J.R. and Munro, S. (2002). Vesicle tethering complexes in membrane traffic. J. Cell Sci. 115, 2627–2637. 2. Barr, F.A. (1999). A novel Rab6-interacting domain defines a family of golgi-targeted coiled-coil proteins. Curr. Biol. 9, 381–384. 3. Kjer-Nielsen, L., Teasdale, R.D., van Vliet, C. and Gleeson, P.A. (1999). A novel golgi-localisation domain shared by a class of coiled-coil peripheral membrane proteins. Curr. Biol. 9, 385–388. 4. Munro, S. and Nichols, B.J. (1999). The GRIP domain - a novel golgi-targeting domain found in several coiled-coil proteins. Curr. Biol. 9, 377–380. 5. Panic, B., Whyte, J.R.C., and Munro, S. (2003). The ARF-like GTPases Arl1p and Arl3p act in a pathway that interacts with vesicle tethering factors at the Golgi apparatus. Curr. Biol. 13, this issue. 6. Gangi Setty, S.R., Shin, M.E., Yoshino, A., Marks, M.S. and Burd, C.G. (2003). Golgi Recruitment of GRIP domain proteins by ARF-like GTPase 1 (Arl1p) is regulated by Arf-like GTPase 3 (Arl3p). Curr. Biol. 13, this issue. 7. Huang, C.F., Buu, L.M., Yu, W.L. and Lee, F.J. (1999). Characterization of a novel ADP-ribosylation factor-like protein (yARL3) in Saccharomyces cerevisiae. J. Biol. Chem. 274, 3819–3827. 8. Lu, L., Horstmann, H., Ng, C. and Hong, W. (2001). Regulation of Golgi structure and function by ARF-like protein 1 (Arl1). J. Cell Sci. 114, 4543–4555. 9. Rosenwald, A.G., Rhodes, M.A., Van Valkenburgh, H., Palanivel, V., Chapman, G., Boman, A., Zhang, C.J. and Kahn, R.A. (2002). ARL1 and membrane traffic in Saccharomyces cerevisiae. Yeast 15, 1039–1056. 10. Van Valkenburgh, H., Shern, J.F., Sharer, J.D., Zhu, X. and Kahn, R.A. (2001). ADP-ribosylation factors (ARFs) and ARF-like 1 (ARL1) have both specific and shared effectors: characterizing ARL1binding proteins. J. Biol. Chem. 276, 22826–22837. 11. Pasqualato, S., Renault, L. and Cherfils, J. (2002). Arf, Arl, Arp and Sar proteins: a family of GTP-binding proteins with a structural device for ‘front-back’ communication. EMBO Rep. 3, 1035–1041. 12. Mueller, A.G., Moser, M., Kluge, R., Leder, S., Blum, M., Buttner, R., Joost, H.G. and Schurmann, A. (2002). Embryonic lethality caused by apoptosis during gastrulation in mice lacking the gene of the ADP-ribosylation factor-related protein 1. Mol. Cell. Biol. 22, 1488–1494.
Dispatch R176
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Tamkun, J.W., Kahn, R.A., Kissinger, M., Brizuela, B.J., Rulka, C., Scott, M.P. and Kennison, J.A. (1991). The arflike gene encodes an essential GTP-binding protein in Drosophila. Proc. Natl. Acad. Sci. U.S.A. 88, 3120–3124. Kooy, J., Toh, B.H., Pettitt, J.M., Erlich, R. and Gleeson, P.A. (1992). Human autoantibodies as reagents to conserved Golgi components: Characterization of a peripheral, 230-kDa compartment-specific Golgi protein. J. Biol. Chem. 267, 20255–20263. Luke, M.R., Kjer-Nielsen, L., Brown, D.L., Stow, J.L. and Gleeson, P.A. (2003). GRIP domain-mediated targeting of two new coiled-coil proteins, GCC88 and GCC185, to subcompartments of the transGolgi network. J. Biol. Chem. 278, 4216–4226. Shorter, J., Beard, M.B., Seemann, J., Dirac-Svejstrup, A.B. and Warren, G. (2002). Sequential tethering of Golgins and catalysis of SNAREpin assembly by the vesicle-tethering protein p115. J. Cell Biol. 157, 45–62. Conibear, E. and Stevens, T.H. (2000). Vps52p, Vps53p and Vps54p form a novel multisubunit complex required for protein sorting at the yeast late Golgi. Mol. Biol. Cell 11, 305–323. Siniossoglou, S. and Pelham, H.R. (2001). An effector of Ypt6p binds the SNARE Tlg1p and mediates selective fusion of vesicles with late Golgi membranes. EMBO J. 20, 5991–5998. Ortiz, D., Medkova, M., Walch-Solimena, C. and Novick, P. (2002). Ypt32 recruits the Sec4p guanine nucleotide exchange factor, Sec2p, to secretory vesicles; evidence for a Rab cascade in yeast. J. Cell Biol. 157, 1005–1015. Wang, W. and Ferro-Novick, S. (2002). A Ypt32p exchange factor is a putative effector of Ypt1p. Mol. Biol. Cell 13, 3336–3343.
Membrane Traffic: Arl GTPases Get a GRIP on the Golgi Catherine L. Jackson
A subset of the golgin family of large coiled-coil proteins have a GRIP domain that mediates their localization to the trans-Golgi. Two recent papers show that the Arl3p and Arl1p small GTPases act sequentially to recruit GRIP domain proteins to the Golgi.
The Golgi apparatus is the central sorting organelle in eukaryotic cells, situated at the intersection of exocytic and endocytic membrane trafficking pathways. Membrane fusion is essential for protein transport through the Golgi, and takes place in several discrete steps that ensure specificity of the final fusion event. The first step is known as tethering, and a number of proteins have been implicated in this process, including the golgins [1]. These large Golgi-localized proteins have an extended coiled-coil conformation, and play an important role in maintaining Golgi structure in all eukaryotic cells from yeast to humans. Previous work showed that a subset of the golgins contain a carboxyterminal region, called the GRIP domain, that mediates binding to Golgi membranes [2–4]. Two papers in this issue of Current Biology have now demonstrated the mechanism by which GRIP domains are recruited to the Golgi [5,6]. These papers show that the small GTPases Arl3p and Arl1p, in their GTP-bound active conformations, act sequentially to recruit GRIP domain proteins to the Golgi in yeast. The Arl proteins themselves had been shown previously to play important roles in trafficking through the Golgi, but the molecular details were not known [7–10]. These results are an important step towards elucidating the molecular mechanisms coordinating Golgi structure with trafficking through this complex organelle. Arl (for ADP-ribosylation factor-like) GTP-binding proteins are a subfamily of the ADP-ribosylation factor (Arf) branch of the small G protein superfamily. The Arl proteins are highly conserved through evolution, and have diverse functions including regulation of membrane trafficking [11]. The yeast Saccharomyces cerevisiae has two Arl proteins, Arl1p and Arl3p, both of which appear to play roles in trafficking in the transGolgi network (TGN)-endosomal system [7,9]. The mammalian homologues of Arl1p and Arl3p are ARL1 and Arf-related protein (ARFRP1), respectively. ARL1 is involved in the regulation of Golgi structure, is localized to the TGN in mammalian cells, and regulates trafficking in the TGN-endosomal system like its yeast counterpart [8,10]. Deletion of ARFRP1 in mice leads to early embryonic lethality and a mutation in Drosophila Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA. E-mail: [email protected]
PII S0960-9822(03)00116-7
Dispatch
ARL1 is zygotic lethal, indicating essential roles for both of these proteins in metazoans [12,13]. The golgins also play an important role in the structure and functioning of the Golgi apparatus in eukaryotic organisms. These proteins were originally identified as the antigens recognized by autoantibodies present in the serum of patients with autoimmune disorders such as Sjögren’s syndrome [14]. Aside from short amino- and carboxy-terminal domains, the golgins are predicted to adopt an extensive coiledcoil conformation (Figure 1A). At least four golgins (p230/golgin-245, golgin-97, GCC88 and GCC185) in mammalian cells, and one (Imh1p) in S. cerevisiae have at their carboxyl terminus a conserved region called the ‘GRIP’ domain, a ~45 amino acid motif necessary and sufficient for localization of these proteins to Golgi membranes, specifically the TGN [2–4,15]. The four mammalian GRIP-domain golgins each show the same response to treatment by the drug brefeldin A (BFA) in that none of these proteins is rapidly released from Golgi membranes (that is, within 2 minutes of treatment). The golgins are only released after approximately 15 minutes of treatment with the drug, the time at which the Golgi disassembles [15]. Hence the membrane association of the golgins depends on an intact Golgi structure, but is not regulated directly by the Arf proteins, which are direct targets of BFA. The new work published in this issue of Current Biology by Panic et al. [5] and Gangi Setty et al. [6] shows that both Arl1p and Arl3p are required for localization of GRIP-domain proteins to Golgi membranes. Arl1p–GTP interacts specifically with the GRIP domain to recruit it to membranes, and Arl3p is required for normal Golgi localization of Arl1p. Gangi Setty et al. [6] show that it is the activated form of Arl3p, Arl3p–GTP, that is required for Arl1p recruitment to Golgi membranes. The GTPase cycle of Arl3p therefore regulates membrane binding of Arl1p, which in turn, through its own GTPase cycle, regulates Golgi localization of the GRIP-domain proteins. Although the results have so far only been demonstrated in yeast, it is likely that these results will hold true for the mammalian homologues, given the conservation of these proteins at both the sequence and functional levels. Indeed, Gangi Setty et al. [6] show that the GRIP domains of human golgin-97 and mouse tGolgin-1 (the mouse homologue of golgin-245) are recruited to the yeast Golgi by Arl1p–GTP in an Arl3p-dependent manner. In addition, previous work demonstrated a two-hybrid interaction between human ARL1-Q71L (the GTPlocked form) and the GRIP domain of human Golgin245, and co-localization of these two proteins in mammalian cells [10]. The golgins have been proposed to act as tethering factors — proteins or protein complexes that act to hold two fusing membranes in place prior to the actual fusion event [16]. There are now a number of protein complexes that appear to be involved in tethering at
Current Biology R175
Figure 1. Arl3p and Arl1p act sequentially to recruit GRIP-domain proteins to the Golgi. (A) Schematic diagram of GRIP domain proteins. p230/golgin-245, golgin-97, GCC88 and GCC185 are mammalian proteins, and Imh1p is the sole GRIP-domain protein in S. cerevisiae. N, amino-terminal region with no coiled-coil propensity; coiled-coil, large central region predicted to adopt a largely coiled-coil conformation; GRIP, GRIP domain. (B) The Arl3p and Arl1p GTPases act sequentially to recruit GRIP domain proteins to Golgi membranes. Both Arl3p–GDP and Arl1p–GDP are localized to the cytoplasm. Upon nucleotide exchange by as yet unidentified GEFs, each is localized to membranes. Arl3p–GTP could recruit Arl1p directly, through interaction with its GEF, or through interaction with another Arl3p effector. Arl1p–GTP then binds to GRIP-domain proteins, recruiting them to the Golgi membrane.
N
A
Coiled-coil
GRIP
Golgin-97 Golgin-245 GCC88 GCC185 Imh1p B
different sites within cells, including the GARP/VFT complex [1]. GARP/VFT (also known as the Vps52-5354 complex) has been implicated in retrograde transport from endosomal compartments back to the TGN in yeast [17]. Panic et al. [5] show that GARP/VFT binds to Arl1p in its GTP-bound form. Previous work had implicated the Rab protein Ypt6p in membrane localization of the GARP/VFT complex in yeast [18], and it may be that the Ypt6p and Arl1p GTPases together coordinate binding of this complex to membranes. However, unlike the case for the GRIP-domain proteins, GARP/VFT localization is not abrogated in an arl1∆ mutant, indicating either that the Arl1p–GARP interaction serves a different role, or that redundant pathways lead to membrane binding of the GARP/VFT complex. One way to test whether Ypt6p and Arl1p act in separate pathways to recruit GARP/VFT to membranes is to assay localization of the complex in a strain deleted for both Ypt6 and Arl1p. Interestingly, both Panic et al. [5] and Gangi Setty et al. [6] have found that such a strain is inviable, so although the simple experiment cannot be done, this result nevertheless shows that Ypt6 and Arl1p have an essential overlapping function. An attractive hypothesis suggested by the results of Panic et al. [5] is that Arl1p–GTP may recruit multiple tethering factors to membranes, perhaps to distinct locations. Future work will no doubt be directed at testing these ideas. Recently, small GTPases of the Rab family have been shown to act in signaling cascades in which an upstream Rab regulates the function of a Rab protein acting downstream in the secretory pathway [19,20]. Ypt32p localizes to the late Golgi at regions of polarized growth in yeast, and binds directly in its GTPbound form to Sec2p, a guanine nucleotide exchange factor (GEF) for the Sec4p Rab GTPase. Ypt32–GTP thus recruits Sec2p to membranes where it activates Sec4p [19]. It is tempting to speculate that a similar mechanism may hold true for Arl3p and Arl1p (Figure 1B). Since the GEFs for these GTPases are not known, testing this hypothesis will await the identification of
trans-Golgi
Arl3–GTP GEF Arl3–GDP
Arl1–GTP ?
GRIP domain protein
GEF Arl1–GDP Current Biology
Arl3p and Arl1p exchange factors. Other possibilities are that Arl1p interacts directly with Arl3p–GTP, or that Arl1p interacts with another effector of Arl3p (Figure 1B). Determining the molecular details of the Arl3p–Arl1p GTPase cascade, and the regulation of the recruitment of GRIP-domain proteins and potentially other tethering factors to membranes will be fertile ground for future experiments. References 1. Whyte, J.R. and Munro, S. (2002). Vesicle tethering complexes in membrane traffic. J. Cell Sci. 115, 2627–2637. 2. Barr, F.A. (1999). A novel Rab6-interacting domain defines a family of golgi-targeted coiled-coil proteins. Curr. Biol. 9, 381–384. 3. Kjer-Nielsen, L., Teasdale, R.D., van Vliet, C. and Gleeson, P.A. (1999). A novel golgi-localisation domain shared by a class of coiled-coil peripheral membrane proteins. Curr. Biol. 9, 385–388. 4. Munro, S. and Nichols, B.J. (1999). The GRIP domain - a novel golgi-targeting domain found in several coiled-coil proteins. Curr. Biol. 9, 377–380. 5. Panic, B., Whyte, J.R.C., and Munro, S. (2003). The ARF-like GTPases Arl1p and Arl3p act in a pathway that interacts with vesicle tethering factors at the Golgi apparatus. Curr. Biol. 13, this issue. 6. Gangi Setty, S.R., Shin, M.E., Yoshino, A., Marks, M.S. and Burd, C.G. (2003). Golgi Recruitment of GRIP domain proteins by ARF-like GTPase 1 (Arl1p) is regulated by Arf-like GTPase 3 (Arl3p). Curr. Biol. 13, this issue. 7. Huang, C.F., Buu, L.M., Yu, W.L. and Lee, F.J. (1999). Characterization of a novel ADP-ribosylation factor-like protein (yARL3) in Saccharomyces cerevisiae. J. Biol. Chem. 274, 3819–3827. 8. Lu, L., Horstmann, H., Ng, C. and Hong, W. (2001). Regulation of Golgi structure and function by ARF-like protein 1 (Arl1). J. Cell Sci. 114, 4543–4555. 9. Rosenwald, A.G., Rhodes, M.A., Van Valkenburgh, H., Palanivel, V., Chapman, G., Boman, A., Zhang, C.J. and Kahn, R.A. (2002). ARL1 and membrane traffic in Saccharomyces cerevisiae. Yeast 15, 1039–1056. 10. Van Valkenburgh, H., Shern, J.F., Sharer, J.D., Zhu, X. and Kahn, R.A. (2001). ADP-ribosylation factors (ARFs) and ARF-like 1 (ARL1) have both specific and shared effectors: characterizing ARL1binding proteins. J. Biol. Chem. 276, 22826–22837. 11. Pasqualato, S., Renault, L. and Cherfils, J. (2002). Arf, Arl, Arp and Sar proteins: a family of GTP-binding proteins with a structural device for ‘front-back’ communication. EMBO Rep. 3, 1035–1041. 12. Mueller, A.G., Moser, M., Kluge, R., Leder, S., Blum, M., Buttner, R., Joost, H.G. and Schurmann, A. (2002). Embryonic lethality caused by apoptosis during gastrulation in mice lacking the gene of the ADP-ribosylation factor-related protein 1. Mol. Cell. Biol. 22, 1488–1494.
Dispatch R176
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Tamkun, J.W., Kahn, R.A., Kissinger, M., Brizuela, B.J., Rulka, C., Scott, M.P. and Kennison, J.A. (1991). The arflike gene encodes an essential GTP-binding protein in Drosophila. Proc. Natl. Acad. Sci. U.S.A. 88, 3120–3124. Kooy, J., Toh, B.H., Pettitt, J.M., Erlich, R. and Gleeson, P.A. (1992). Human autoantibodies as reagents to conserved Golgi components: Characterization of a peripheral, 230-kDa compartment-specific Golgi protein. J. Biol. Chem. 267, 20255–20263. Luke, M.R., Kjer-Nielsen, L., Brown, D.L., Stow, J.L. and Gleeson, P.A. (2003). GRIP domain-mediated targeting of two new coiled-coil proteins, GCC88 and GCC185, to subcompartments of the transGolgi network. J. Biol. Chem. 278, 4216–4226. Shorter, J., Beard, M.B., Seemann, J., Dirac-Svejstrup, A.B. and Warren, G. (2002). Sequential tethering of Golgins and catalysis of SNAREpin assembly by the vesicle-tethering protein p115. J. Cell Biol. 157, 45–62. Conibear, E. and Stevens, T.H. (2000). Vps52p, Vps53p and Vps54p form a novel multisubunit complex required for protein sorting at the yeast late Golgi. Mol. Biol. Cell 11, 305–323. Siniossoglou, S. and Pelham, H.R. (2001). An effector of Ypt6p binds the SNARE Tlg1p and mediates selective fusion of vesicles with late Golgi membranes. EMBO J. 20, 5991–5998. Ortiz, D., Medkova, M., Walch-Solimena, C. and Novick, P. (2002). Ypt32 recruits the Sec4p guanine nucleotide exchange factor, Sec2p, to secretory vesicles; evidence for a Rab cascade in yeast. J. Cell Biol. 157, 1005–1015. Wang, W. and Ferro-Novick, S. (2002). A Ypt32p exchange factor is a putative effector of Ypt1p. Mol. Biol. Cell 13, 3336–3343.