Myosin II isoforms play distinct roles in adherens junction biogenesis

Abstract

Adherens junction (AJ) assembly under force is essential for many biological processes like epithelial monolayer bending, collective cell migration, cell extrusion and wound healing. The acto-myosin cytoskeleton acts as a major force-generator during the de novo formation and remodeling of AJ. Here, we investigated the role of non-muscle myosin II isoforms (NMIIA and NMIIB) in epithelial junction assembly. NMIIA and NMIIB differentially regulate biogenesis of AJ through association with distinct actin networks. Analysis of junction dynamics, actin organization, and mechanical forces of control and knockdown cells for myosins revealed that NMIIA provides the mechanical tugging force necessary for cell-cell junction reinforcement and maintenance. NMIIB is involved in E-cadherin clustering, maintenance of a branched actin layer connecting E-cadherin complexes and perijunctional actin fibres leading to the building-up of anisotropic stress. These data reveal unanticipated complementary functions of NMIIA and NMIIB in the biogenesis and integrity of AJ.

Multiscale analysis of single and double maternal-zygotic Myh9 and Myh10 mutants during mouse preimplantation development

“…We observe reduced compaction when Myh9 is maternally deleted and slower compaction when Myh10 is deleted (Fig 1A-B). This is in agreement with cell culture studies, in which Myh9 knockdown reduces contact size whereas Myh10 knockdown does not [30,31]. This is also in agreement with previous studies using inhibitory drugs on the preimplantation embryo.…”

“…For example, Myh9 plays a key role in setting the speed of furrow ingression during cytokinesis [27,28] and is essential to drive bleb retraction [29]. During cell-cell contact formation, Myh9 was found essential for cadherin adhesion molecule clustering and setting contact size while Myh10 would be involved in force transmissions across the junction and would influence contact rearrangements [30,31].…”

MAGIs regulate aPKC to enable balanced distribution of intercellular tension for epithelial sheet homeostasis

“…Two isoforms of non-muscle myosin II, NMIIA and NMIIB, localize to the epithelial AJC 7 . While both isoforms are necessary for the mechanical integrity of epithelial junctions, NMIIB is considered the dominant generator of force at AJC and is required for sustaining high tension along the cell-cell interface 7,38 . Therefore, we examined NMIIB localization in our knockout cell models.…”

The distinct roles of myosin IIA and IIB under compression stress in nucleus pulposus cells

“…For example, in epithelial junction assembly, myosin IIA is parallel to the junction and provides mechanical force for the maintenance of adherens junction. Myosin IIB localizes at junctional membranes and organizes the junctional branched actin meshwork 18 . A recent study demonstrated that myosin IIA is dedicated to generating cortex tension for faster cleavage furrow ingression in cell division, while myosin IIB acts as a stabilizing motor by reducing cortex tension 19 .…”