Chondroitin sulfate and cytoplasmic domain-dependent membrane targeting of the NG2 proteoglycan promotes retraction fiber formation and cell polarization.
Targeting of the NG2 proteoglycan to cellular retraction fibers was studied by expressing mutant NG2 molecules lacking specific structural elements of the proteoglycan. Both the cytoplasmic domain and the chondroitin sulfate chain of NG2 appear to have roles in sorting NG2 to subcellular microdomains destined to become retraction fibers. Neither of these structural features alone is sufficient to allow optimal targeting of NG2 to retraction fibers, but together they promote efficient localization of the proteoglycan to these sites. This pattern of NG2 sorting seems to be necessary for optimal retraction fiber formation, as cells expressing poorly targeted NG2 mutants are noticeably deficient in their ability to extend retraction fibers. Furthermore, retraction fiber formation correlates strongly with the tendency of cells to assume a polarized morphology with NG2-positive retraction fibers at one pole of the cell and actin-rich lamellipodia at the other. This polarization can be triggered either through engagement of NG2 by the substratum or by exposure to lysophosphatidic acid, a potent activator of the rho GTPase. These results suggest a possible role for NG2 in regulating rho-dependent mechanisms in the trailing processes of motile cells.
Stallcup
W B
WB
The Burnham Institute, La Jolla Cancer Research Center, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Dahlin-Huppe
K
K
D000818:Animals; D000941:Antigens / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002462:Cell Membrane / Q000378:metabolism*; D016764:Cell Polarity; D002809:Chondroitin Sulfates / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism*; D006801:Humans; D008856:Microscopy, Fluorescence; D017354:Point Mutation; D021381:Protein Transport; D011509:Proteoglycans / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D012694:Serine / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D002809:Chondroitin Sulfates; D011509:Proteoglycans; D012694:Serine; D020741:rho GTP-Binding Proteins; D000099216:Chondroitin Sulfate Proteoglycan 4