HMP-1/α-catenin promotes junctional mechanical integrity during morphogenesis

Abstract

Adherens junctions (AJs) are key structures regulating tissue integrity and maintaining adhesion between cells. During morphogenesis, junctional proteins cooperate closely with the actomyosin network to drive cell movement and shape changes. How the junctions integrate the mechanical forces in space and in time during an in vivo morphogenetic event is still largely unknown, due to a lack of quantitative data. To address this issue, we inserted a functional Fluorescence Resonance Energy Transfer (FRET)-based force biosensor within HMP-1/α-catenin of Caenorhabditis elegans. We find that the tension exerted on HMP-1 has a cell-specific distribution, is actomyosin-dependent, but is regulated differently from the tension on the actin cortex during embryonic elongation. By using time-lapse analysis of mutants and tissue-specific rescue experiments, we confirm the role of VAB-9/Claudin as an actin bundle anchor. Nevertheless, the tension exerted on HMP-1 did not increase in the absence of VAB-9/Claudin, suggesting that HMP-1 activity is not upregulated to compensate for loss of VAB-9. Our data indicate that HMP-1 does not modulate HMR-1/E-cadherin turnover, is required to recruit junctional actin but not stress fiber-like actin bundles. Altogether, our data suggest that HMP-1/α-catenin acts to promote the mechanical integrity of adherens junctions.

Game of Tissues: How the Epidermis Thrones C. elegans Shape

“…Thus, while the cells are restructuring their apical junctions, the basolateral membranes are relieving the tension generated in CeAJs through protrusive activity [85]. In accordance, a FRET-based force sensor placed in the HMP-1 gene, revealed that the tension exerted at the CeAJs decrease by 1.3-to 1.5-fold even though cells are experiencing high actomyosin contraction, supporting the idea that membrane protrusion acts as a tension relieving mechanism [54,[84][85][86]. Adding to tension-relieving mechanisms, junction strengthening also provides a means by which cells can reinforce tension resistance.…”

“…Consequently, cell-cell adhesion is unbalanced by an unequal distribution of pulling forces. This lowers resistance to tension, resulting in rupture and aborted elongation [15,16,84]. In the same line, Martin and colleagues propose that differential employment of actomyosin regulatory pathways by the epidermal subtypes may simultaneously relieve tension.…”

“…They showed that dorsal cells use the RAC-1 mediated pathway to generate lamellipodia-like protrusions below the level of the CeAJs towards the seam cells while the seam cells use the RHO-1 mediated pathway to induce the formation of amoeboid-like protrusions in the direction of the dorsal cells. At the same time, the myosin activity controlled by these pathways regulates the remodeling of the CeAJs, where an increased myosin activity correlates with a decreased junctional length [84,85]. Thus, while the cells are restructuring their apical junctions, the basolateral membranes are relieving the tension generated in CeAJs through protrusive activity [85].…”

A Genetically Encoded Biosensor Strategy for Quantifying Non-muscle Myosin II Phosphorylation Dynamics in Living Cells and Organisms

“…Biosensor imaging has been applied to classic models of embryonic development less frequently than whole animal physiology, with only a handful of successes reported in zebrafish (Andrews et al, 2016; Muto et al, 2011; Xu et al, 2012; Zhao et al, 2015), Drosophila (Markova et al, 2015), and C. elegans (Kelley et al, 2015; Vuong-Brender et al, 2018). Consequently, less is known about protein activities during development outside of gene expression.…”

Multifunctional roles of Tropomodulin-3 in regulating actin dynamics

“…HMP-1/-catenin is a component of the cadherin-catenin complex that protects epidermal adherens junctions from contractile stresses imposed by circumferential actomyosin bundles during embryonic morphogenesis (Vuong-Brender et al 2018). UNC-94 is localized to the adherens junction in proximity to, but not directly interacting with, HMP-1 (Cox-Paulson et al 2012;Stevenson et al 2007).…”