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 α4(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. © 2003 Wiley‐Liss, Inc.