Snapin interacts with the Exo70 subunit of the exocyst and modulates GLUT4 trafficking.
The exocyst is a multisubunit complex that has been implicated in the transport of vesicles from the Golgi complex to the plasma membrane, possibly acting as a vesicle tether and contributing to the specificity of membrane fusion. Here we characterize a novel interaction between the Exo70 subunit of the exocyst and Snapin, a ubiquitous protein known to associate with at least two t-SNAREs, SNAP23 and SNAP25. The interaction between Exo70 and Snapin is mediated via an N-terminal coil-coil domain in Exo70 and a C-terminal helical region in Snapin. Exo70 competes with SNAP23 for Snapin binding, suggesting that Snapin does not provide a direct link between the exocyst and the SNARE complex but, rather, mediates cross-talk between the two complexes by sequential interactions. The insulin-regulated trafficking of GLUT4 to the plasma membrane serves to facilitate glucose uptake in adipocytes, and both SNAP23 and the exocyst have been implicated in this process. In this study, depletion of Snapin in adipocytes using RNA interference inhibits insulin-stimulated glucose uptake. Thus, Snapin interacts with the exocyst and plays a modulatory role in GLUT4 vesicle trafficking.
Bao
Yiqun
Y
Epithelial Cell Biology Laboratory, Institute of Molecular and Cell Biology, 61 Biopolis Drive, Singapore 138673, Singapore and the.
Lopez
Jamie A
JA
Diabetes and Obesity Research Program, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst New South Wales, Sydney 2010, Australia.
James
David E
DE
Diabetes and Obesity Research Program, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst New South Wales, Sydney 2010, Australia. Electronic address: d.james@garvan.org.au.
Hunziker
Walter
W
Epithelial Cell Biology Laboratory, Institute of Molecular and Cell Biology, 61 Biopolis Drive, Singapore 138673, Singapore and the. Electronic address: hunziker@imcb.a-star.edu.sg.
D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002522:Chlorocebus aethiops; D020868:Gene Silencing; D005947:Glucose / Q000378:metabolism / Q000493:pharmacokinetics; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D051379:Mice; D018613:Microscopy, Confocal; D041681:NIH 3T3 Cells; D011485:Protein Binding; D021381:Protein Transport / Q000187:drug effects; D050766:Qb-SNARE Proteins / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D020798:Two-Hybrid System Techniques; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*
C522783:Exo70 protein, mouse; D051275:Glucose Transporter Type 4; D007328:Insulin; D050766:Qb-SNARE Proteins; D034741:RNA, Small Interfering; C498451:Snapin protein, mouse; D033921:Vesicular Transport Proteins; D005947:Glucose