Asundi Vinod K, Erdman Robert, Stahl Richard C, Carey David J
Weis Center for Research, Geisinger Clinic, Danville, Pennsylvania 17822-2601, USA.
J Neurosci Res. 2003 Sep 1;73(5):593-602. doi: 10.1002/jnr.10699.
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.
在胚胎后期和出生后早期的外周神经发育阶段，施万细胞短暂表达跨膜硫酸乙酰肝素蛋白聚糖syndecan-3。新生大鼠施万细胞通过一种被内源性基质金属蛋白酶活性抑制所阻断的过程，将可溶性syndecan-3释放到培养基中。当施万细胞接种在结合syndecan-3的基质上时，释放的蛋白聚糖会结合到细胞边界附近的基质上。膜锚定的syndecan-3集中在从施万细胞膜边缘伸出的含肌动蛋白的丝状伪足中。膜脱落对syndecan-3具有特异性，而相关蛋白聚糖syndecan-1则未观察到这种现象。对转染了野生型和嵌合型syndecan-1及syndecan-3 cDNA的施万细胞进行分析发现，膜脱落是syndecan-3胞外结构域的一种特性。抑制syndecan-3的释放显著增强了施万细胞在涂有α4(V)胶原非胶原N端结构域的培养皿上的黏附及突起生长，该结构域可结合syndecan-3并介导硫酸乙酰肝素依赖性施万细胞黏附。在新生大鼠外周神经组织中也观察到了基质金属蛋白酶依赖性的syndecan-3脱落。外周神经组织中的syndecan-3脱落具有年龄特异性，在出生后神经发育的后期阶段未观察到。这些结果表明，施万细胞syndecan-3会经历基质金属蛋白酶依赖性的膜加工过程，这一过程会调节这种蛋白聚糖的生物学功能。
