Differential cellular responses to adhesive interactions with galectin-8- and fibronectin-coated substrates.

Wenhong Li,Jürgen Groll,Ohad Medalia,Yehiel Zick,Benjamin Geiger,Alexander D Bershadsky,Ana Sancho,Yaron Vinik,Wen-Lu Chung

doi:10.1242/jcs.252221

Abstract

ABSTRACTThe mechanisms underlying the cellular response to extracellular matrices (ECMs) that consist of multiple adhesive ligands are still poorly understood. Here, we address this topic by monitoring specific cellular responses to two different extracellular adhesion molecules – the main integrin ligand fibronectin and galectin-8, a lectin that binds β-galactoside residues − as well as to mixtures of the two proteins. Compared with cell spreading on fibronectin, cell spreading on galectin-8-coated substrates resulted in increased projected cell area, more-pronounced extension of filopodia and, yet, the inability to form focal adhesions and stress fibers. These differences can be partially reversed by experimental manipulations of small G-proteins of the Rho family and their downstream targets, such as formins, the Arp2/3 complex and Rho kinase. We also show that the physical adhesion of cells to galectin-8 was stronger than adhesion to fibronectin. Notably, galectin-8 and fibronectin differently regulate cell spreading and focal adhesion formation, yet act synergistically to upregulate the number and length of filopodia. The physiological significance of the coherent cellular response to a molecularly complex matrix is discussed.This article has an associated First Person interview with the first author of the paper.

Highlights

In multicellular organisms, the majority of cells interact with the extracellular matrix (ECM), a multi-molecular network comprising the cells’ microenvironment (Cárcamo et al, 2006; Diskin et al, 2012)
Different dynamics of filopodia and lamellipodia extensions of cells grown on fibronectin and galectin-8 HeLa cell spreading manifests itself primarily in the continuous extension of two types of membrane protrusion, filopodia and lamellipodia
On galectin-8, cell spreading was initiated by the formation of filopodia (Fig. 1B,C; Movies 2 and 3), which was rapidly succeeded by the formation of lamellipodia

Summary

Introduction

The majority of cells interact with the extracellular matrix (ECM), a multi-molecular network comprising the cells’ microenvironment (Cárcamo et al, 2006; Diskin et al, 2012). Several classes of cell surface receptor interact with the ECM, and convey to cells its biochemical and mechanical characteristics. Depending on the type of matrix and the specific cellular context, matrix receptors assemble into different types of adhesion complexes through which they interact with the cytoskeleton Adhesion complexes, such as focal adhesions (Geiger et al, 2009), podosomes (Alonso et al, 2019; Schachtner et al, 2013), hemidesmosomes (Walko et al, 2015), filopodia (Jacquemet et al, 2015) and adhesion waves (Case and Waterman, 2011) are formed by several hundreds of structural and signaling proteins, which collectively mediate the adhesive and signaling functions of these structures

Methods

Results

Conclusion