A dual role for IQGAP1 in regulating exocytosis.
Polarized secretion is a tightly regulated event generated by conserved, asymmetrically localized multiprotein complexes, and the mechanism(s) underlying its temporal and spatial regulation are only beginning to emerge. Although yeast Iqg1p has been identified as a positional marker linking polarity and exocytosis cues, studies on its mammalian counterpart, IQGAP1, have focused on its role in organizing cytoskeletal architecture, for which the underlying mechanism is unclear. Here, we report that IQGAP1 associates and co-localizes with the exocyst-septin complex, and influences the localization of the exocyst and the organization of septin. We further show that activation of CDC42 GTPase abolishes this association and inhibits secretion in pancreatic beta-cells. Whereas the N-terminus of IQGAP1 binds the exocyst-septin complex, enhances secretion and abrogates the inhibition caused by CDC42 or the depletion of IQGAP1, the C-terminus, which binds CDC42, inhibits secretion. Pulse-chase experiments indicate that IQGAP1 influences protein-synthesis rates, thus regulating exocytosis. We propose and discuss a model in which IQGAP1 serves as a conformational switch to regulate exocytosis.
Rittmeyer
Eric N
EN
Department of Microbiology, Cornell University, Ithaca, NY 14853-2703, USA.
Daniel
Samira
S
Hsu
Shu-Chan
SC
Osman
Mahasin A
MA
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D016764:Cell Polarity; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D005089:Exocytosis / Q000502:physiology*; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008954:Models, Biological; D046912:Multiprotein Complexes; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D058112:Septins; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020703:ras GTPase-Activating Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
D003598:Cytoskeletal Proteins; C522783:Exo70 protein, mouse; C101203:IQ motif containing GTPase activating protein 1; D046912:Multiprotein Complexes; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D033921:Vesicular Transport Proteins; D020703:ras GTPase-Activating Proteins; D010744:Phosphoric Monoester Hydrolases; D020558:GTP Phosphohydrolases; C106863:Sept2 protein, mouse; D058112:Septins; D020764:cdc42 GTP-Binding Protein