αE-catenin regulates cell-cell adhesion and membrane blebbing during zebrafish epiboly

Abstract

SUMMARYE-catenin is an actin-binding protein associated with the E-cadherin-based adherens junction that regulates cell-cell adhesion.Recent studies identified additional E-cadherin-independent roles of E-catenin in regulating plasma membrane dynamics and cell migration. However, little is known about the roles of E-catenin in these different cellular processes in vivo during early vertebrate development. Here, we examined the functions of E-catenin in cell-cell adhesion, cell migration and plasma membrane dynamics during morphogenetic processes that drive epiboly in early Danio rerio (zebrafish) development. We show that depletion of E-catenin caused a defect in radial intercalation that was associated with decreased cell-cell adhesion, in a similar manner to E-cadherin depletion. Depletion of E-catenin also caused deep cells to have protracted plasma membrane blebbing, and a defect in plasma membrane recruitment of ERM proteins that are involved in controlling membrane-to-cortex attachment and membrane blebbing. Significantly, depletion of both E-cadherin and E-catenin suppressed plasma membrane blebbing. We suggest that during radial intercalation the activities of E-cadherin and E-catenin in the maintenance of membrane-to-cortex attachment are balanced, resulting in stabilization of cell-cell adhesion and suppression of membrane blebbing, thereby enabling proper radial intercalation.

E-cadherin is under constitutive actomyosin-generated tension that is increased at cell–cell contacts upon externally applied stretch

“…In this context, it is noteworthy that cadherin lateral mobility in the plasma membrane depends on the catenin-binding region of the cytoplasmic domain even outside of cell-cell contacts and is regulated by the underlying cortical actin cytoskeleton (54,55). That the cadherin/catenin complex functions in membrane-to-cortex attachment may explain why this complex is important for regulating macropinocytosis in contact-free protruding membranes (56), single-cell wound closure in Drosophila (57), and plasma membrane blebbing during early embryogenesis in zebrafish (58). Plasma membrane blebbing involves functional crosstalk between the cadherin/catenin complex and ezrin-radixin-moesin (ERM) proteins (58), which also mediate membrane-to-cortex attachment (59).…”

“…That the cadherin/catenin complex functions in membrane-to-cortex attachment may explain why this complex is important for regulating macropinocytosis in contact-free protruding membranes (56), single-cell wound closure in Drosophila (57), and plasma membrane blebbing during early embryogenesis in zebrafish (58). Plasma membrane blebbing involves functional crosstalk between the cadherin/catenin complex and ezrin-radixin-moesin (ERM) proteins (58), which also mediate membrane-to-cortex attachment (59). Although the molecular events directly downstream of E-cadherin tension remain unclear, E-cadherin, and likely αE-catenin, may be involved in a ubiquitous tension-sensing mechanism that regulates cortical cytoskeleton activity as a function of cell shape, size, or membrane activity.…”

Danio rerio αE-catenin Is a Monomeric F-actin Binding Protein with Distinct Properties from Mus musculus αE-catenin

“…Do these differences in biochemical properties of M. musculus ␣E-catenin and D. rerio ␣E-catenin reflect differences in loss-of-function phenotypes in the mouse and zebrafish, respectively? Loss of ␣E-catenin function in mammals (3)(4)(5)(6)(7) and zebrafish (34) leads to a decrease in cadherin-mediated cell-cell adhesion. However, in mammals, loss of ␣E-catenin increases Arp2/3 complex-dependent lamellipodial dynamics (5,14), whereas in zebrafish, D. rerio ␣E-catenin depletion increases membrane blebbing (34).…”

How blebs and pseudopods cooperate during chemotaxis

“…Blebbing is important in cells migrating in three-dimensional environments, such as during tumor invasion (6,7), zebrafish primordial germ cell migration (8,9), or migration of the pathogen Entamoeba histolytica in the liver (10). Dictyostelium amoebae can also move with blebs (11).…”