Journal
JOURNAL OF CELL BIOLOGY
Volume 168, Issue 4, Pages 655-666Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200411158
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Funding
- NCRR NIH HHS [P51 RR000163, RR00163, K01 RR000163] Funding Source: Medline
- NIGMS NIH HHS [GM60432, R01 GM060432] Funding Source: Medline
- NINDS NIH HHS [NS39550, R01 NS040759, NS40759] Funding Source: Medline
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Schwann cells form basal laminae (BLs) containing laminin-2 (Ln-2; heterotrimer alpha2beta1gamma1) and Ln-8 (alpha4beta1gamma1). Loss of Ln-2 in humans and mice carrying alpha2-chain mutations prevents developing Schwann cells from fully defasciculating axons, resulting in partial amyelination. The principal pathogenic mechanism is thought to derive from structural defects in Schwann cell BLs, which Ln-2 scaffolds. However, we found loss of Ln-8 caused partial amyelination in mice without affecting BL structure or Ln-2 levels. Combined Ln-2/Ln-8 deficiency caused nearly complete amyelination, revealing Ln-2 and -8 together have a dominant role in defasciculation, and that Ln-8 promotes myelination without BLs. Transgenic Ln-10 (alpha5beta1gamma1) expression also promoted myelination without BL formation. Rather than BL structure, we found Ln-2 and -8 were specifically required for the increased perinatal Schwann cell proliferation that attends myelination. Purified Ln-2 and -8 directly enhanced in vitro Schwann cell proliferation in collaboration with autocrine factors, suggesting Lns control the onset of myelination by modulating responses to mitogens in vivo.
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