Dynamin 2 orchestrates the global actomyosin cytoskeleton for epithelial maintenance and apical constriction

Jennifer Chua, Richa Rikhy, Jennifer Lippincott-Schwartz
Proceedings of the National Academy of Sciences of the United States of America 2009 December 8, 106 (49): 20770-5
The mechanisms controlling cell shape changes within epithelial monolayers for tissue formation and reorganization remain unclear. Here, we investigate the role of dynamin, a large GTPase, in epithelial morphogenesis. Depletion of dynamin 2 (Dyn2), the only dynamin in epithelial cells, prevents establishment and maintenance of epithelial polarity, with no junctional formation and abnormal actin organization. Expression of Dyn2 mutants shifted to a non-GTP state, by contrast, causes dramatic apical constriction without disrupting polarity. This is due to Dyn2's interactions with deacetylated cortactin and downstream effectors, which cause enhanced actomyosin contraction. Neither inhibitors of endocytosis nor GTP-shifted Dyn2 mutants induce apical constriction. This suggests that GTPase-dependent changes in Dyn2 lead to interactions with different effectors that may differentially modulate endocytosis and/or actomyosin dynamics in polarized cells. We propose this enables Dyn2 to coordinate, in a GTPase-dependent manner, membrane recycling and actomyosin contractility during epithelial morphogenesis.

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