Matrix metalloproteinase-dependent shedding of syndecan-3, a transmembrane heparan sulfate proteoglycan, in Schwann cells.
Schwann cells transiently express the transmembrane heparan sulfate proteoglycan syndecan-3 during the late embryonic and early postnatal periods of peripheral nerve development. Neonatal rat Schwann cells released soluble syndecan-3 into the culture medium by a process that was blocked by inhibition of endogenous matrix metalloproteinase activity. When Schwann cells were plated on a substratum that binds syndecan-3, the released proteoglycan bound to the substratum adjacent to the cell border. Membrane-anchored syndecan-3 was concentrated in actin-containing filopodia that projected from the lateral edges of the Schwann cell membrane. Membrane shedding was specific for syndecan-3 and was not observed for the related proteoglycan syndecan-1. Analysis of Schwann cells transfected with wild-type and chimeric syndecan-1 and syndecan-3 cDNAs revealed that membrane shedding was a property of the syndecan-3 ectodomain. Inhibition of syndecan-3 release significantly enhanced Schwann cell adhesion and process extension on dishes coated with the non-collagenous N-terminal domain of alpha4(V) collagen, which binds syndecan-3 and mediates heparan sulfate-dependent Schwann cell adhesion. Matrix metalloproteinase-dependent syndecan-3 shedding was also observed in newborn rat peripheral nerve tissue. Syndecan-3 shedding in peripheral nerve tissue was age specific, and was not observed during later stages of postnatal nerve development. These results demonstrate that Schwann cell syndecan-3 is subject to matrix metalloproteinase-dependent membrane processing, which modulates the biological function of this proteoglycan.
Asundi
Vinod K
VK
Weis Center for Research, Geisinger Clinic, Danville, Pennsylvania 17822-2601, USA.
Erdman
Robert
R
Stahl
Richard C
RC
Carey
David J
DJ
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000032:analysis / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D010525:Peripheral Nerves / Q000737:chemistry / Q000254:growth & development* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011509:Proteoglycans / Q000032:analysis / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D012583:Schwann Cells / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D053670:Syndecan-3; D014162:Transfection
D004791:Enzyme Inhibitors; D019812:Heparan Sulfate Proteoglycans; D061965:Matrix Metalloproteinase Inhibitors; D008562:Membrane Glycoproteins; D011509:Proteoglycans; C508303:Sdc3 protein, rat; D053670:Syndecan-3; D020782:Matrix Metalloproteinases