α7 integrin in muscular dystrophy

By contrast, the inhibitory activity of Kssl p identified in this paper is independent of its protein kinase activity. The authors made mutants of Kssl p that would cause a hyperfilamentous growth phenotype and identified those that retained this ability even when the Ksslp protein kinase activity was abolished by mutation or that did not require the Kssl p-activating kinaseSte7p for the effect. The kinaseindependent inhibitory effect of Kssl p appears to be mediated by binding to Ste12p (the transcription factor). Similarly, Fus3p is shown to be the protein kinase involved in pheromone signalling. Finally, Fus3p is found to inhibit both the growth switch and activation of the pheromone pathway by Kssl p, in a manner that is independent of the protein kinase activity of Fus3p. Protein-phosphorylationindependent effects of protein kinases have been referred to in these columns before, but this is the first time that they have been shown to be important in vivo. To summarize, Ksslp promotes filamentous growth; Fus3p signals mating. Fus3p and Ksslp inhibit the Ksslp switch in a novel, protein-kinase-activity-independent fashion. As a yeast bard might say, 'If phosphorylation be for food or love, play on'!

integrin in muscular dystrophy MAYER, U. et al. (1997) Absence of integrin ~7 causes a novel form of muscular dystrophy Nat. Genet. 17, 318-323 VACHON, P. et aL (1997) Integrins (~7131) in muscle function and survival. Disrupted expression in merosin-deficient congenital muscular dystrophy J. Clin. Invest. 100, 1870-1881 One of the hottest topics in muscular dystrophy research today concerns the role of different membrane receptors in muscular dystrophy. The myospheroid mutation in Drosophila is embryonic lethal and is characterized by detachment of muscles from their attachment points. In the late 198Os, it was shown the MYOSPHEROID protein is an integrin beta chain. The phenotype of the myospheroid mutation indicated for the first time that integrins are important for the mechanical stability of muscles. That this holds true in vertebrate muscles is shown elegantly by Mayer et al., who inactivated the gene encoding the ~7 integrin in mice. Muscle ~7 integrin is enriched at the major site of force transmission - the myotendinous junction. Mice deficient in ~7 integrin that survive the embryonic period develop a novel type of muscular dystrophy characterized by defects at the myotendinous junction. The parallel with Drosophila is striking and shows that the mechanism for forming muscle attachments is conserved during development. Ligands for the ~7 integrin are found within the laminin family. Major laminin isoforms in adult muscle include laminin-2 and laminin-4, which both incorporate the laminin ~2 chain. A very interesting paper from the group of E. Engvall (Vachon et al.) investigates the effect of lack of laminin ~2. This study was performed in dystrophic 56

mice with reduced levels of the laminin ~2 chain and in human congenital muscular dystrophy patients with defects in the laminin c~2 chain. In both cases, the distribution of the dystroglycan complex is unaffected by the defective laminin e~2 levels, whereas the normal distribution of ~7131 integrin is disrupted. These data indicate that the distribution the ~7131 integrin is more dependent on the presence of laminin ~2 than is the dystroglycan complex. This is the first clue that there are different mechanisms determining the distribution of the ~7131 integrin and dystroglycan complex and opens up several new interesting avenues for future research. Obvious questions now are whether there is another ligand for dystroglycan in the basement membrane or whether dystroglycan localization is independent of ligand binding.

Another bacterial transporter in chloroplasts SE1-FLES,A. M., YONETANI, A., BARON, A., BUSH, D. R., CLINE, K. and MARTIENSSEN, R. (1997) Sec-independent protein translocation by the maize Hcf106 protein Science 278, 1467-1470 Protein targeting to the thylakoids within chloroplasts has long been an enigmatic process. While the mechanism for proteins crossing the chloroplast envelope membranes is the same for almost every protein examined, at least four different pathways have been identified for polypeptides passing into or across the thylakoid membrane. Two of these pathways are clearly based on ancestral bacterial protein export pathways, involving a signal recognition particle (SRP)54-kDa homologue in one case and Sec protein homologues in the other. A third pathway, which is powered by the thylakoid transmembrane pH gradient and which is targeted by signal sequences containing a unique RR motif, has until now been considered to be unique, without a bacterial counterpart. This paper suggests that this is not the case. The RR signal sequence motif has been recognized previously in certain bacterial proteins residing in the periplasm [Berks, B. C. (1996) MoL Microbiol. 22, 393-404]. These proteins often have redox functions and carry prosthetic groups that might be attached before the proteins are exported, raising intriguing questions about the conformation of the translocated substrate. Here, Settleset al. furthered the characterization of a maize mutant, hall 06, that was shown previously to be defective in the thylakoid delta-pH-dependent protein-targeting pathway [Voelker, R. and Barkan, A. (1995) EMBO J. 14, 3905-3914], and they report the sequence of the responsible gene. Searching the genetic databases, they identified hypothetical open reading frame (ORF) homologues of HCF106 in a number of bacteria. Remarkably,the homologous ORF in an Azotobactergene is located in an operon that is essentialfor hydrogen-dependent respiration, which itself requires the transport of a subunit with an RR signal sequence. Furthermore, a knockout of the HCF106 homoIogue in this organism is reported to result in mislocalization of its hydrogenase activity. trends in CELLBIOLOGY(Vol. 8) February1998