Schwann cells synthesize type V collagen that contains a novel alpha 4 chain - Molecular cloning, biochemical characterization, and high affinity heparin binding of alpha 4(V) collagen

Previously, we reported the isolation of a heparan sulfate-binding collagen ous protein, p200, that is expressed by Schwann cells in developing periphe ral nerves ((1996) J, Biol, Chem, 271, 13844-13853; (1999) J. Neurosci. Res . 56, 284-294), Here, we report the cloning of p200 cDNA from a Schwann cel l cDNA library. The deduced amino acid sequence identifies p200 as a novel member of the collagen type V gene family. This polypeptide, which me have named alpha 4 type V (alpha 4(V)) collagen, contains an uninterrupted GIS-X -X collagen domain of 1011 amino acids that shows 82% sequence identity to human alpha 3(V) collagen and 71% identity to rat alpha 1(V) collagen. alph a 4(V) is secreted by Schwann cells as a collagen heterotrimer that also co ntains alpha 1(V) chains. alpha 4(V)-containing collagen molecules synthesi zed by Schmann cells retain their amino-terminal non-collagenous domains. a lpha 4(V) mRNA was detected by reverse transcriptase-linked polymerase chai n reaction amplification in neonatal and adult brain and neonatal periphera l nerve. alpha 4(V) mRNA and protein were not detected in most other tissue s, including the placenta and heart, which are known to contain alpha 3(V). This pattern of alpha 4(V) expression contrasted with that of alpha 1(V) m RNA and protein, which were ubiquitously expressed. The isolated alpha 4(V) chain demonstrated an unusually high affinity for heparin, The restricted expression and unusual properties of alpha 4(V)-containing collagen type V molecules suggest a unique and important role for these molecules in periph eral nerve development.