Cellular prion protein interaction with vitronectin supports axonal growth and is compensated by integrins
Cellular prion protein interaction with vitronectin supports axonal growth and is compensated by integrins
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DOI：
10.1242/jcs.03459
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发表时间：
2007-06-01
影响因子：
4
通讯作者：
Martins, Vilma R.
中科院分区：
文献类型：
--
作者：
Hajj, Glaucia N. M.;Lopes, Marilene H.;Martins, Vilma R.
细胞朊蛋白PrPC作为一种细胞表面多效性受体的生理功能目前还存在争议。我们报告说，PrPC相互作用与玻连蛋白，但不与纤维连接蛋白或胶原蛋白。介导这种PrPC-玻连蛋白相互作用的结合位点被定位到PrPC的残基105-119和玻连蛋白的残基307-320。这两种蛋白质共定位于胚胎背根神经节从野生型小鼠。玻连蛋白除了培养的背根神经节诱导轴突生长，这可以模拟玻连蛋白肽307-320和废除抗PrPC抗体。全长玻连蛋白，但不是玻连蛋白肽307-320，诱导轴突生长的背根神经元从两个品系的PrPC-null小鼠。功能测定表明，相对于野生型细胞，PrPC-null背根神经元更响应于Arg-Gly-Asp肽（整合素结合位点），并表现出更大的α v β 3活性。我们的研究结果表明，PrPC在轴突生长中起着重要的作用，这种功能可能是拯救PrPC基因敲除动物的整合素代偿机制。
The physiological functions of the cellular prion protein, PrPC, as a cell surface pleiotropic receptor are under debate. We report that PrPC interacts with vitronectin but not with fibronectin or collagen. The binding sites mediating this PrPC-vitronectin interaction were mapped to residues 105-119 of PrPC and the residues 307-320 of vitronectin. The two proteins were co-localized in embryonic dorsal root ganglia from wild-type mice. Vitronectin addition to cultured dorsal root ganglia induced axonal growth, which could be mimicked by vitronectin peptide 307-320 and abrogated by anti-PrPC antibodies. Full-length vitronectin, but not the vitronectin peptide 307-320, induced axonal growth of dorsal root neurons from two strains of PrPC-null mice. Functional assays demonstrated that relative to wild-type cells, PrPC-null dorsal root neurons were more responsive to the Arg-Gly-Asp peptide (an integrin-binding site), and exhibited greater alpha v beta 3 activity. Our findings indicate that PrPC plays an important role in axonal growth, and this function may be rescued in PrPC-knockout animals by integrin compensatory mechanisms.