科研之友
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摘要
During development, Schwann cells extend lamellipodia-like processes to segregate large- and small-caliber axons during the process of radial sorting. Radial sorting is a prerequisite for myelination and is arrested in human neuropathies because of laminin deficiency. Experiments in mice using targeted mutagenesis have confirmed that laminins 211, 411, and receptors containing the beta 1 integrin subunit are required for radial sorting; however, which of the 11 alpha integrins that can pair with beta 1 forms the functional receptor is unknown. Here we conditionally deleted all the alpha subunits that form predominant laminin-binding beta 1 integrins in Schwann cells and show that only alpha 6 beta 1 and alpha 7 beta 1 integrins are required and that alpha 7 beta 1 compensates for the absence of alpha 6 beta 1 during development. The absence of either alpha 7 beta 1 or alpha 6 beta 1 integrin impairs the ability of Schwann cells to spread and to bind laminin 211 or 411, potentially explaining the failure to extend cytoplasmic processes around axons to sort them. However, double alpha 6/alpha 7 integrin mutants show only a subset of the abnormalities found in mutants lacking all beta 1 integrins, and a milder phenotype. Double-mutant Schwann cells can properly activate all the major signaling pathways associated with radial sorting and show normal Schwann cell proliferation and survival. Thus, alpha 6 beta 1 and alpha 7 beta 1 are the laminin-binding integrins required for axonal sorting, but other Schwann cell beta 1 integrins, possibly those that do not bind laminins, may also contribute to radial sorting during peripheral nerve development.
- 出版日期2013-11-13
