Adherens junctions connect stress fibres between adjacent endothelial cells

Abstract

BackgroundEndothelial cell-cell junctions maintain endothelial integrity and regulate vascular morphogenesis and homeostasis. Cell-cell junctions are usually depicted with a linear morphology along the boundaries between adjacent cells and in contact with cortical F-actin. However, in the endothelium, cell-cell junctions are highly dynamic and morphologically heterogeneous.ResultsWe report that endothelial cell-cell junctions can attach to the ends of stress fibres instead of to cortical F-actin, forming structures that we name discontinuous adherens junctions (AJ). Discontinuous AJ are highly dynamic and are increased in response to tumour necrosis factor (TNF)-α, correlating with the appearance of stress fibres. We show that vascular endothelial (VE)-cadherin/β-catenin/α-catenin complexes in discontinuous AJ are linked to stress fibres. Moreover, discontinuous AJ connect stress fibres from adjacent cells independently of focal adhesions, of which there are very few in confluent endothelial cells, even in TNF-α-stimulated cells. RNAi-mediated knockdown of VE-cadherin, but not zonula occludens-1, reduces the linkage of stress fibres to cell-cell junctions, increases focal adhesions, and dramatically alters the distribution of these actin cables in confluent endothelial cells.ConclusionsOur results indicate that stress fibres from neighbouring cells are physically connected through discontinuous AJ, and that stress fibres can be stabilized by AJ-associated multi-protein complexes distinct from focal adhesions.

Gene(s) and individual feeding behavior: Exploring eco‐evolutionary dynamics underlying left‐right asymmetry in the scale‐eating cichlid fishPerissodus microlepis

“…While previous studies failed to validate a former candidate locus (UNH2101; Lee et al., 2015, 2010; Stewart & Albertson, 2010 but note the use of different methods to estimate asymmetry), here, we confirmed the association between the locus located in a genomic region containing immunoglobulin genes and mouth polymorphism. Specifically, the SNP 56537‐113 is related to mouth asymmetry whether this is expressed as a continuous trait (mouth bending angle, this study) or as a categorical variable (L and R morphs, Raffini et al., 2017).…”

“…The first aim of this study was to validate this SNP by testing its association with asymmetry using a larger sample size and Sanger sequencing, which has a lower sequencing error. Additionally, while previous studies investigated genomic loci underlying the difference between L and R morphs (i.e., the direction of mouth asymmetry, Hori, 1993; Hori et al., 2007; Lee et al., 2015; Palmer, 2010; Raffini et al., 2017; Stewart & Albertson, 2010), here, for the first time we extend this work by analyzing the association between the candidate locus and mouth bending angle, a more precise and continuous quantification of asymmetry.…”

“…Three main explanations have been proposed to date: strictly genetic (due to a single Mendelian locus, Hori, 1993; Hori, Ochi, & Kohda, 2007; Stewart & Albertson, 2010), totally or partially random (Palmer, 2004, 2010), and multifactorial (Lee et al., 2015; Palmer, 2010; Raffini, Fruciano, Franchini, & Meyer, 2017; Stewart & Albertson, 2010; Van Dooren et al., 2010) determination of mouth asymmetry. The first two models are hard to reconcile with multiple findings that emerged in the last decade: a) unimodal distribution of mouth shape in both adults and larvae (Kusche et al., 2012; Lee et al., 2015; Stewart & Albertson, 2010; Van Dooren et al., 2010), which is not consistent with a single Mendelian locus; b) parents‐offspring frequencies that do not match expectations for a trait controlled by a single simple locus or a partially random determination of the direction of laterality as seen in mice's internal asymmetry (Lee et al., 2015; Palmer, 2010); c) a significant heritability or single‐nucleotide polymorphisms (SNPs) significantly associated with laterality (Lee et al., 2015; Raffini et al., 2017), which are incompatible with a purely random basis of mouth asymmetry; d) evidence for trait plasticity (Kusche et al., 2012; Lee et al., 2012; Takeuchi et al., 2016; Van Dooren et al., 2010), which is inconsistent with a strictly genetic basis. Mouth asymmetry in P. microlepis then is a complex trait (third model, Lee et al., 2015; Palmer, 2010; Raffini et al., 2017; Stewart & Albertson, 2010; Van Dooren et al., 2010), whose variation is most likely due to a polygenic basis and non‐genetic factors (Kusche et al., 2012; Lee et al., 2012; Raffini et al., 2017; Stewart & Albertson, 2010; Takeuchi & Oda, 2017; Takeuchi et al., 2016; Van Dooren et al., 2010).…”

“…Several studies suggested that mouth asymmetry in P. microlepis has a sizable genetic component (Hori, 1993; Hori et al., 2007; Lee et al., 2015; Palmer, 2010; Raffini et al., 2017; Stewart & Albertson, 2010). This leads to the question: which regions of the genome contain the gene(s) responsible for asymmetry?…”

“…This leads to the question: which regions of the genome contain the gene(s) responsible for asymmetry? A microsatellite locus was suggested to be linked to a putative laterality gene (Stewart & Albertson, 2010), but subsequent studies failed to confirm this association (Lee et al., 2010, 2015). More recently, we conducted a genome‐wide study that identified several SNPs potentially related to mouth asymmetry (Raffini et al., 2017).…”