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Reach out and gRab something

Rab6 (blue) and Arl1 (gray) cooperate to bind GCC185 (green), a vesicle- transporting tether. PFEFFER/ELSEVIER

When families cooperate, their effects can be far reaching, according to Suzanne Pfeffer (Stanford University, Stanford, CA) and colleagues, whose study of Rab6 and Arl1 shows that these members of different GTPase families work together to anchor a vesicle-tethering protein onto the Golgi.

The tethering protein, GCC185, is thought to bind to transport vesicles destined for the Golgi. GCC185 contains a GRIP domain, which is known to bind to a possible anchor at the Golgi called Arl1. But previous work showed that Arl1 only bound weakly, if at all, to GCC185.

Since Rab6 is another tether-linking Golgi protein, the authors looked in detail at its possible interactions with GCC185. They found a pair of Rab6-binding sites just distal to those for Arl1 on GCC185. When Rab6 bound the tether first, Arl1 bound much more strongly. "Nobody expected that two different classes of GTPases would work cooperatively to localize this protein," Pfeffer says.

The structure of the complex suggests how they may cooperate. Rab6 has a long tail that enables it to reach up to 100 Å away from the membrane to grab onto distant GCC185. Once Rab6 latches onto the tether, Arl1 binds it closer in to secure it in place. "It may be a molecular handoff," says Pfeffer. Once the protein passes into the "GRIP" of Arl1, Rab6 is free to reach out and grab some more.

Reference:

Burguete, A.S., et al. 2008. Cell. 132:286–298.[CrossRef][Medline]

Richard Robinson

rrobinson{at}nasw.org

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This Article Full Text (PDF, 1129K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Robinson, R. Search for Related Content PubMed Articles by Robinson, R. Social Bookmarking                            What's this?