The Adaptor Protein Lurap1 Is Required for Cell Cohesion during Epiboly Movement in Zebrafish

Abstract

Cell adhesion and polarized cellular behaviors play critical roles in a wide variety of morphogenetic events. In the zebrafish embryo, epiboly represents an important process of epithelial morphogenesis that involves differential cell adhesion and dynamic cell shape changes for coordinated movements of different cell populations, but the underlying mechanism remains poorly understood. The adaptor protein Lurap1 functions to link myotonic dystrophy kinase-related Rac/Cdc42-binding kinase with MYO18A for actomyosin retrograde flow in cell migration. We previously reported that it interacts with Dishevelled in convergence and extension movements during gastrulation. Here, we show that it regulates blastoderm cell adhesion and radial cell intercalation during epiboly. In zebrafish mutant embryos with loss of both maternal and zygotic Lurap1 function, deep cell multilayer of the blastoderm exhibit delayed epiboly with respect to the superficial layer. Time-lapse imaging reveals that these deep cells undergo unstable intercalation, which impedes their expansion over the yolk cell. Cell sorting and adhesion assays indicate reduced cellular cohesion of the blastoderm. These defects are correlated with disrupted cytoskeletal organization in the cortex of blastoderm cells. Thus, the present results extend our previous works by demonstrating that Lurap1 is required for cell adhesion and cell behavior changes to coordinate cell movements during epithelial morphogenesis. They provide insights for a further understanding of the regulation of cytoskeletal organization during gastrulation cell movements.

Emerging concepts of myosin 18A isoform mechanobiology in organismal and immune system physiology, development, and function

“…Li et al. have also implicated LURAP1 and MYO18A in mediating cell adhesion during epiboly movement during vertebrate embryogenesis, a fascinating potential role for both proteins 65 . In this context, Newman et al.…”

“…Li et al have also implicated LURAP1 and MYO18A in mediating cell adhesion during epiboly movement during vertebrate embryogenesis, a fascinating potential role for both proteins. 65 In this context, Newman et al reported that MYO18Aα operates at three-dimensional level to convey integrin-associated cell-matrix interactions with nuclear movement through MYH9 across the cell. 23 Work by Yu and colleagues identified the interaction of MYO18Aɑ with the p21-activated kinase 2 (PAK2) via binding of the carboxy-terminal extension of MYO18Aɑ with the PAK-interacting exchange factor βPIX.…”

“…The MYO18A‐MYH9 interaction may be involved in the localization of MYO18A binding partners to cytoskeletal filaments through direct and indirect interactions of cytoskeleton signaling modifiers LURAP1, MRCK, βPIX, p190GEF, and GOLPH3. These modifiers engage the RhoGTPases RAC1, RAC2, and CDC42 and their effector kinases PAK1 and PAK2 mediating membrane and MYH9‐dependent cytoskeleton remodeling, and lateral interactions between cells, and cell‐matrix interactions 15,63–66 …”