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Dev Cell ; 34(2): 139-151, 2015 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-26166299

RESUMO

During CNS development, oligodendrocytes wrap their plasma membrane around axons to generate multilamellar myelin sheaths. To drive growth at the leading edge of myelin at the interface with the axon, mechanical forces are necessary, but the underlying mechanisms are not known. Using an interdisciplinary approach that combines morphological, genetic, and biophysical analyses, we identified a key role for actin filament network turnover in myelin growth. At the onset of myelin biogenesis, F-actin is redistributed to the leading edge, where its polymerization-based forces push out non-adhesive and motile protrusions. F-actin disassembly converts protrusions into sheets by reducing surface tension and in turn inducing membrane spreading and adhesion. We identified the actin depolymerizing factor ADF/cofilin1, which mediates high F-actin turnover rates, as an essential factor in this process. We propose that F-actin turnover is the driving force in myelin wrapping by regulating repetitive cycles of leading edge protrusion and spreading.


Assuntos
Actinas/metabolismo , Sistema Nervoso Central/crescimento & desenvolvimento , Cofilina 1/metabolismo , Destrina/metabolismo , Bainha de Mielina/fisiologia , Citoesqueleto de Actina/fisiologia , Actinas/biossíntese , Animais , Axônios/fisiologia , Adesão Celular/fisiologia , Membrana Celular/fisiologia , Células Cultivadas , Sistema Nervoso Central/embriologia , Cofilina 1/genética , Destrina/genética , Proteínas Luminescentes , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Oligodendroglia/citologia , Técnicas de Patch-Clamp , Tensão Superficial , Peixe-Zebra , Proteína Vermelha Fluorescente
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