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 collagenous protein, p200, that is expressed by Schwann cells in developing peripheral 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 cell cDNA library. The deduced amino acid sequence identifies p200 as a novel member of the collagen type V gene family. This polypeptide, which we have named alpha4 type V (alpha4(V)) collagen, contains an uninterrupted Gly-X-X collagen domain of 1011 amino acids that shows 82% sequence identity to human alpha3(V) collagen and 71% identity to rat alpha1(V) collagen. alpha4(V) is secreted by Schwann cells as a collagen heterotrimer that also contains alpha1(V) chains. alpha4(V)-containing collagen molecules synthesized by Schwann cells retain their amino-terminal non-collagenous domains. alpha4(V) mRNA was detected by reverse transcriptase-linked polymerase chain reaction amplification in neonatal and adult brain and neonatal peripheral nerve. alpha4(V) mRNA and protein were not detected in most other tissues, including the placenta and heart, which are known to contain alpha3(V). This pattern of alpha4(V) expression contrasted with that of alpha1(V) mRNA and protein, which were ubiquitously expressed. The isolated alpha4(V) chain demonstrated an unusually high affinity for heparin. The restricted expression and unusual properties of alpha4(V)-containing collagen type V molecules suggest a unique and important role for these molecules in peripheral nerve development.
Chernousov
M A
MA
Sigfried and Janet Weis Center for Research, Geisinger Clinic, Danville, Pennsylvania 17822, USA.
Rothblum
K
K
Tyler
W A
WA
Stahl
R C
RC
Carey
D J
DJ
D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D001205:Ascorbic Acid / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D003001:Cloning, Molecular; D003094:Collagen / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D009928:Organ Specificity; D020033:Protein Isoforms / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification; D012583:Schwann Cells / Q000187:drug effects / Q000378:metabolism*; D012584:Sciatic Nerve / Q000378:metabolism
D046911:Macromolecular Substances; D020033:Protein Isoforms; D011994:Recombinant Proteins; D006493:Heparin; D003094:Collagen; D001205:Ascorbic Acid