An evolutionary and physiological perspective on cell-substrate adhesion machinery for cell migration

Abstract

Cell-substrate adhesion is a critical aspect of many forms of cell migration. Cell adhesion to an extracellular matrix (ECM) generates traction forces necessary for efficient migration. One of the most well-studied structures cells use to adhere to the ECM is focal adhesions, which are composed of a multilayered protein complex physically linking the ECM to the intracellular actin cytoskeleton. Much of our understanding of focal adhesions, however, is primarily derived from in vitro studies in Metazoan systems. Though these studies provide a valuable foundation to the cell-substrate adhesion field, the evolution of cell-substrate adhesion machinery across evolutionary space and the role of focal adhesions in vivo are largely understudied within the field. Furthering investigation in these areas is necessary to bolster our understanding of the role cell-substrate adhesion machinery across Eukaryotes plays during cell migration in physiological contexts such as cancer and pathogenesis. In this review, we review studies of cell-substrate adhesion machinery in organisms evolutionary distant from Metazoa and cover the current understanding and ongoing work on how focal adhesions function in single and collective cell migration in an in vivo environment, with an emphasis on work that directly visualizes cell-substrate adhesions. Finally, we discuss nuances that ought to be considered moving forward and the importance of future investigation in these emerging fields for application in other fields pertinent to adhesion-based processes.

Reduced PaxillinB localization to cell-substrate adhesions promotes cell migration inDictyostelium

“…Interestingly, homology analyses of core focal adhesion components suggest Dictyostelium possess putative homologues of some but not all components (Fierro Morales et al, 2022;Sebe-Pedros et al, 2010), indicating that Dictyostelium is able to use focal adhesion-based migration despite lacking core components thought to be pivotal for proper focal adhesion formation and function. Though this body of research indicates Dictyostelium forms focal adhesions for efficient migration -much like in mesenchymal cells -Dictyostelium single cell migration is associated with amoeboid migration and often used as a comparative model for other amoeboid cells such as leukocytes (Devreotes and Zigmond, 1988;Friedl et al, 2001;Fukui and Inoue, 1997;Paluch et al, 2016).…”

“…This cycle in turn promotes efficient mesenchymal cell migration (referred to as adhesion-based migration going forward) (Geiger et al, 2009; Lock et al, 2008; Oakes and Gardel, 2014). There is extensive literature dissecting focal adhesions during adhesion-based migration, and the majority has focused on mesenchymal cells in flat, in vitro 2D systems (Fierro Morales et al, 2022). These studies have led to an established model of focal adhesion components, assembly, and dynamics characterized by large, mature focal adhesion structures that generate traction forces and a slower rate of migration compared to other forms of motility such as amoeboid migration (Case and Waterman, 2015; Gardel et al, 2010; Kanchanawong et al, 2010; Liu et al, 2015; Pankova et al, 2010; Parsons et al, 2010).…”

“…Classically, focal-adhesion based migration has been considered unique to Metazoans while amoeboid motility is found across Eukaryotes (Brunet et al, 2021; Devreotes and Zigmond, 1988; Fritz-Laylin et al, 2017; Fritz-Laylin and Titus, 2023; Velle and Fritz-Laylin, 2019; Velle and Fritz-Laylin, 2020). Interestingly, while the focal adhesion machinery itself was originally believed to be a Metazoan-specific innovation, genomic analysis of non-Metazoan organisms identified putative homologues of various core components of focal adhesions in organisms as evolutionarily distant as Amoebozoa, suggesting that this machinery originated prior to the divergence of Metazoa (Fierro Morales et al, 2022; Hynes and Zhao, 2000; Rokas, 2008; Sebe-Pedros et al, 2010). Furthermore, focal adhesion homologues are present in non-Metazoan species that are believed to predominantly use focal adhesion-independent migration (ie.…”

“…Studies investigating focal adhesion-like structures in Dictyostelium suggest these amoebae are capable of forming actin-rich adhesion structures that contain homologues of several focal adhesion proteins (Berman et al, 2000; Bukharova et al, 2005; Cornillon et al, 2008; Cornillon et al, 2006; Cornillon et al, 2000; Duran et al, 2009; Fey et al, 2002; Froquet et al, 2012; Hibi et al, 2004; Nagasaki et al, 2009; Niewohner et al, 1997; Patel et al, 2008; Plak et al, 2016; Pribic et al, 2011; Tsujioka et al, 2004; Tsujioka et al, 2008), and generate traction forces on the substratum during migration, reminiscent of focal adhesions (Copos et al, 2017; Iwadate and Yumura, 2008a; Mijanovic and Weber, 2022; Uchida and Yumura, 2004). Interestingly, homology analyses of core focal adhesion components suggest Dictyostelium possess putative homologues of some but not all components (Fierro Morales et al, 2022; Sebe-Pedros et al, 2010), indicating that Dictyostelium is able to use focal adhesion-based migration despite lacking core components thought to be pivotal for proper focal adhesion formation and function.…”

Transcriptome analysis reveals temporally regulated genetic networks duringDrosophilaborder cell collective migration

“…Among the top categories of differentially expressed genes in border cells were adhesion- and morphogenesis-related genes. A variety of adhesion proteins help collectively migrating cells stay together, maintain their cell shapes, communicate among cells, and move upon other cells and extracellular matrices [67; 68; 69]. Similarly, border cells require complex regulation of cell-cell adhesions for their collective migration to maintain cluster integrity and shape as well as to migrate on and between nurse cells [20; 67; 19; 23; 6].…”