A molecular network for the transport of the TI-VAMP/VAMP7 vesicles from cell center to periphery.
The compartmental organization of eukaryotic cells is maintained dynamically by vesicular trafficking. SNARE proteins play a crucial role in intracellular membrane fusion and need to be targeted to their proper donor or acceptor membrane. The molecular mechanisms that allow for the secretory vesicles carrying the v-SNARE TI-VAMP/VAMP7 to leave the cell center, load onto microtubules, and reach the periphery to mediate exocytosis are largely unknown. Here, we show that the TI-VAMP/VAMP7 partner Varp, a Rab21 guanine nucleotide exchange factor, interacts with GolginA4 and the kinesin 1 Kif5A. Activated Rab21-GTP in turn binds to MACF1, an actin and microtubule regulator, which is itself a partner of GolginA4. These components are required for directed movement of TI-VAMP/VAMP7 vesicles from the cell center to the cell periphery. The molecular mechanisms uncovered here suggest an integrated view of the transport of vesicles carrying a specific v-SNARE toward the cell surface.
Institut Jacques Monod, UMR 7592, CNRS, Université Paris Diderot, Sorbonne Paris Cité, Paris, France. burgo.andrea@ijm.univ-paris-diderot.fr
Andrea
A
Burgo
Véronique
V
Proux-Gillardeaux
Emmanuel
E
Sotirakis
Philippe
P
Bun
Alessandra
A
Casano
Agathe
A
Verraes
Ronald K H
RK
Liem
Etienne
E
Formstecher
Maïté
M
Coppey-Moisan
Thierry
T
Galli
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D006056:Golgi Apparatus / Q000378:metabolism*; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism; D015739:Nocodazole / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology*; D050683:R-SNARE Proteins / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D050257:Tubulin Modulators / Q000494:pharmacology
C500506:KIF5A protein, human; D050683:R-SNARE Proteins; D034741:RNA, Small Interfering; D050257:Tubulin Modulators; C121241:VAMP7 protein, human; D016547:Kinesins; D015739:Nocodazole