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

The 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 f...

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Authors: Li, W. (Wenhong)|||/items/36b9bebf-53a0-4e0f-bed7-59eb86663a79, Sancho-Erkizia, A. (Ana)|||/items/846a5cef-75df-48f7-a906-d9ede56961f9, Chung, W.L. (Wen-Lu)|||/items/2f8c6899-3875-4746-b232-12239de1a20e, Vinik, Y. (Yaron)|||/items/69e4eeb0-38cd-4ef6-ae94-9b38ec347737, Groll, J. (Jürgen)|||/items/e8a87b25-4fe7-42fd-9410-5c0432c774c5, Zick, Y. (Yehiel)|||/items/d53f8a02-16db-4a35-8dac-70b7d0eb6aab, Medalia, O. (Ohad)|||/items/21d6037c-82ce-494e-ad45-3f617a46a4bf, Bershadsky, A.D. (Alexander D.)|||/items/97d72d2f-cbd9-4984-9a65-97da316d9e66, Geiger, B. (Benjamin)|||/items/9fbbeb6c-6d51-463e-89ab-ff49fb1282e0
Format: article
Publication Date:2021
Country:España
Institution:Universidad de Navarra
Repository:Dadun. Depósito Académico Digital de la Universidad de Navarra
Language:English
OAI Identifier:oai:dadun.unav.edu:10171/120480
Online Access:https://hdl.handle.net/10171/120480
Access Level:Open access
Keyword:Extracellular matrix
Filopodia
Focal adhesions
Lamellipodia
Myosin-II
Rho GTPases
Description
Summary:The 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.