CD98hc (SLC3A2) participates in fibronectin matrix assembly by mediating integrin signaling.
Integrin-dependent assembly of the fibronectin (Fn) matrix plays a central role in vertebrate development. We identify CD98hc, a membrane protein, as an important component of the matrix assembly machinery both in vitro and in vivo. CD98hc was not required for biosynthesis of cellular Fn or the maintenance of the repertoire or affinity of cellular Fn binding integrins, which are important contributors to Fn assembly. Instead, CD98hc was involved in the cell's ability to exert force on the matrix and did so by dint of its capacity to interact with integrins to support downstream signals that lead to activation of RhoA small GTPase. Thus, we identify CD98hc as a membrane protein that enables matrix assembly and establish that it functions by interacting with integrins to support RhoA-driven contractility. CD98hc expression can vary widely; our data show that these variations in CD98hc expression can control the capacity of cells to assemble an Fn matrix, a process important in development, wound healing, and tumorigenesis.
Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Chloé C
CC
Féral
Andries
A
Zijlstra
Eugene
E
Tkachenko
Gerald
G
Prager
Margaret L
ML
Gardel
Marina
M
Slepak
Mark H
MH
Ginsberg
D000818:Animals; D053595:Embryonic Stem Cells; D005353:Fibronectins / Q000378:metabolism*; D027282:Fusion Regulatory Protein 1, Heavy Chain / Q000378:metabolism*; D016023:Integrins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D005353:Fibronectins; D027282:Fusion Regulatory Protein 1, Heavy Chain; D016023:Integrins; C523212:Slc3A2 protein, mouse; D020742:rhoA GTP-Binding Protein