A dual role for IQGAP1 in regulating exocytosis

Abstract

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 β-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.

The Different Strategies Used by Salmonella to Invade Host Cells

“…In addition, it could be interesting to better characterize the role of the cellular factor IQGAP1 which is required for Salmonella uptake and acts following an interaction with actin and the RhoGTPases Rac1 and Cdc42 . Indeed, IQGAP1 is known to regulate actin architecture and interestingly, it also seems to act as a regulator of exocytosis by interacting with Exo70 (Rittmeyer et al, 2008). IQGAP1 could thus be one of the missing links between actin rearrangement and membrane fusion during Salmonella entry.…”

The epithelial polarity program: machineries involved and their hijacking by cancer

“…Matrix metalloprotease accumulation at specific points of contact may require polarized vesicle trafficking. Recently, Chavrier and collaborators showed that the exocyst regulates the exocytosis of matrix metalloproteases in invasive breast carcinoma cells in combination with the Cdc42 effector IQGAP1, the expression of which is highly increased in a variety of cancers (Rittmeyer et al, 2008;Sakurai-Yageta et al, 2008).…”

IQGAP scaffold proteins are the multifunctional regulators of cellular signaling and malignant transformation

“…В свою очередь перестройка актина в значительной степени опреде-ляет подвижность клеток и их способность к миграции [16][17][18]. Другой функцией, выполняемой локализо-ванным на мембране IQGAP1 в околомембранном пространстве, является модуляция экзоцитоза [19]. Поскольку в процессе экзоцитоза в околоклеточное пространство выбрасываются в том числе и матрикс-ные протеиназы, IQGAP1 может быть регулятором перестроек внеклеточного матрикса и ассоциирован-ной с ними клеточной инвазии [20].…”