Coordinate control of axon defasciculation and myelination by laminin-2 and -8.
J Cell Biol
; 168(4): 655-66, 2005 Feb 14.
Article
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| MEDLINE
| ID: mdl-15699217
ABSTRACT
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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Bases de datos:
MEDLINE
Asunto principal:
Células de Schwann
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Axones
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Membrana Basal
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Laminina
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Vaina de Mielina
Límite:
Animals
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Humans
Idioma:
En
Revista:
J Cell Biol
Año:
2005
Tipo del documento:
Article
País de afiliación:
Estados Unidos