A Unique Role for Nonmuscle Myosin Heavy Chain IIA in Regulation of Epithelial Apical Junctions
Year: 2007
Type: article
Abstract: The integrity and function of the epithelial barrier is dependent on the apical junctional complex (AJC) composed of tight and adherens junctions and regulated by the underlying actin filaments. A major F-actin motor, myosin II, was previously implicated in regulation of the AJC, however direct evidence of the involvement of myosin II in AJC dynamics are lacking and the molecular identity of the myosin II motor that regulates formation and disassembly of apical junctions in mammalian epithelia is unknown. We investigated the role of nonmuscle myosin II (NMMII) heavy chain isoforms, A, B, and C in regulation of epithelial AJC dynamics and function. Expression of the three NMMII isoforms was observed in model intestinal epithelial cell lines, where all isoforms accumulated within the perijunctional F-actin belt. siRNA-mediated downregulation of NMMIIA, but not NMMIIB or NMMIIC expression in SK-CO15 colonic epithelial cells resulted in profound changes of cell morphology and cell-cell adhesions. These changes included acquisition of a fibroblast-like cell shape, defective paracellular barrier, and substantial attenuation of the assembly and disassembly of both adherens and tight junctions. Impaired assembly of the AJC observed after NMMIIA knock-down involved dramatic disorganization of perijunctional actin filaments. These findings provide the first direct non-pharmacological evidence of myosin II-dependent regulation of AJC dynamics in mammalian epithelia and highlight a unique role of NMMIIA in junctional biogenesis.
Source: PLoS ONE
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,382
Awards: Intestinal mucosal wound resealing, G172889844, Emory Epithelial Pathobiology Research Development Center, G2194866839, G2378209405, G2385350559, Structure function studies in intestinal epithelial JAM, G4031416708, G4700760395, G4956501685, Role of signal regulatory protein in neutrophil function, Neutrophil Interactions with Intestinal Epithelial Cells, INTESTINAL MUCOSAL WOUND RESEALING IN SURGICAL DISEASES, G6783429524, G727825831, G753365945, Regulation of intestinal epithelial barrier function by intercellular junction proteins in health and disease
OpenAlex ID: W2002167899