First published online January 23, 2008
Journal of Cell Science 121, 303e (2008)
© The Company of Biologists Limited
Polarized growth: IQGAP1 shows the way
During migration, exocytic vesicles fuse with the cell's leading edge to enable directional growth. This polarized secretion is thought to be promoted by the exocyst complex – which tethers vesicles to the plasma membrane – and by septin proteins that associate with the exocyst. However, little is known about how the process is regulated. Now, Mahasin Osman and colleagues (p. 391) propose that the actin-modulating protein IQGAP1 activates polarised secretion. Using co-immunoprecipitation, the authors show that the N-terminal region of IQGAP1 binds the exocyst-septin complex directly in pancreatic β-cells. This interaction is disrupted by the expression of the GTPase CDC42, which is known to bind the C-terminal region of IQGAP1. Moreover, CDC42 also inhibits IQGAP1-mediated insulin secretion. The authors propose, therefore, that IQGAP1 regulates exocytosis by switching between two conformations: CDC42-bound (secretion off) and exocyst-bound (secretion on). The authors go on to demonstrate that IQGAP1 promotes protein synthesis and interacts with the ER translocon. These results implicate IQGAP1 as a major regulator of cell migration and growth.
Related articles in JCS:
- A dual role for IQGAP1 in regulating exocytosis
- Eric N. Rittmeyer, Samira Daniel, Shu-Chan Hsu, and Mahasin A. Osman
JCS 2008 121: 391-403.
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