Two separate metalloproteinase activities are responsible for the shedding and processing of the NG2 proteoglycan in vitro.
A high proportion of NG2 in the adult rat spinal cord is saline-soluble and migrates slightly faster than intact NG2 on SDS-PAGE, suggesting that it represents the shed ectodomain of NG2. In the injured cerebral cortex, much of the overall increase in NG2 is due to the saline-soluble (shed), rather than the detergent-soluble (intact), form. Hydroxamic acid metalloproteinase inhibitors, but not TIMPs, were able to prevent NG2 shedding in oligodendrocyte precursor cells (OPCs) in vitro. The generation of another truncated form of NG2 was, however, sensitive to TIMP-2 and TIMP-3. Two observations suggest that NG2 is involved in PDGF signaling in OPCs: the rate of NG2 shedding increased with cell density and NG2 expression was increased in the absence of PDGF. Ectodomain shedding converts NG2 into a diffusible entity able to interact with the growth cone, and we suggest that this release is likely to enhance its axon growth-inhibitory activity.
Asher
Richard A
RA
Cambridge Centre for Brain Repair, University of Cambridge, Forvie Site, Robinson Way, Cambridge, CB2 2PY, UK. raa24@cam.ac.uk
Morgenstern
Daniel A
DA
Properzi
Francesca
F
Nishiyama
Akiko
A
Levine
Joel M
JM
Fawcett
James W
JW
D000818:Animals; D000941:Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001369:Axons / Q000201:enzymology; D002478:Cells, Cultured; D005260:Female; D020439:Growth Cones / Q000201:enzymology; D066298:In Vitro Techniques; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology; D017434:Protein Structure, Tertiary; D011509:Proteoglycans / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012965:Sodium Chloride; D012995:Solubility; D013116:Spinal Cord / Q000166:cytology* / Q000201:enzymology*; D013234:Stem Cells / Q000166:cytology / Q000648:ultrastructure; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000378:metabolism; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D008666:Metalloendopeptidases; D011509:Proteoglycans; D012965:Sodium Chloride; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D019717:Tissue Inhibitor of Metalloproteinase-3; D000099216:Chondroitin Sulfate Proteoglycan 4