Dynamin 2 orchestrates the global actomyosin cytoskeleton for epithelial maintenance and apical constriction.
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.
Chua
Jennifer
J
Cell Biology and Metabolism Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Rikhy
Richa
R
Lippincott-Schwartz
Jennifer
J
D000205:Actomyosin / Q000378:metabolism*; D000818:Animals; D016764:Cell Polarity; D051356:Cortactin / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism*; D004285:Dogs; D034285:Dynamin II / Q000737:chemistry / Q000378:metabolism*; D004705:Endocytosis; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D050505:Mutant Proteins / Q000378:metabolism; D024462:Myosin Type II / Q000378:metabolism; D009711:Nucleotides / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D019108:Tight Junctions / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D051356:Cortactin; D050505:Mutant Proteins; D009711:Nucleotides; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D000205:Actomyosin; D024462:Myosin Type II; D020741:rho GTP-Binding Proteins; D034285:Dynamin II