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 main...

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Bibliographic Details
Published in:The Journal of cell biology 2007-08, Vol.178 (4), p.701-711
Main Authors: Féral, Chloé C., Zijlstra, Andries, Tkachenko, Eugene, Prager, Gerald, Gardel, Margaret L., Slepak, Marina, Ginsberg, Mark H.
Format: Article
Language:English
Subjects:
Animals
Antibodies
Cell culture techniques
Cells
Cellular biology
Embryonic cells
Embryonic Stem Cells
Endothelial cells
Epithelial cells
Extracellular matrix
Fibronectins - metabolism
Fusion Regulatory Protein 1, Heavy Chain - metabolism
Gene expression
Integrins
Integrins - metabolism
Lymphocytes
Matrix
Membranes
Mice
Mice, Inbred BALB C
Mice, Nude
Proteins
rhoA GTP-Binding Protein - metabolism
Tumors
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Summary: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.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.200705090