Cell surface nucleolin on developing muscle is a potential ligand for the axonal receptor protein tyrosine phosphatase-sigma.
Cell surface nucleolin on developing muscle is a potential ligand for the axonal receptor protein tyrosine phosphatase-sigma.
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DOI：
10.1111/j.1742-4658.2006.05471.x
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发表时间：
2006-10
期刊：
影响因子：
--
通讯作者：
Stoker AW
中科院分区：
文献类型：
--
作者：
Alete DE;Weeks ME;Hovanession AG;Hawadle M;Stoker AW
由受体酪氨酸激酶和受体酪氨酸磷酸酶催化的可逆酪氨酸磷酸化在轴突发育期间的细胞信号传导中起重要作用。受体蛋白酪氨酸磷酸酶PTPσ与视网膜轴突的轴突生长、引导和修复有关。这种磷酸酶也与运动轴突生长和神经支配有关。PTPσ的昆虫直向同源物也涉及肌肉靶细胞的识别。脊椎动物PTPσ的潜在细胞外配体先前已定位于发育中的骨骼肌中。这种肌肉配体的身份目前尚不清楚，但似乎与PTPσ的硫酸乙酰肝素配体无关。在这项研究中，我们已经使用亲和层析和串联质谱鉴定骨骼肌组织中作为PTPσ结合伴侣的核仁素。来自组织裂解物和纯化形式的核仁素都与PTPσ胞外域结合。它的表达模式与以前定位在肌肉中的PTPσ-结合伴侣的表达模式重叠，我们证明了大量的肌肉相关核仁素存在于发育中的肌管的细胞表面。此外，两种核仁素结合组分，乳铁蛋白和HB-19肽，可以阻断PTPσ探针与组织切片中肌肉的相互作用。这些数据表明，细胞表面相关的核仁素是PTPσ的肌肉结合位点的潜在组分，并且可以在细胞表面接近轴突PTPσ。
Reversible tyrosine phosphorylation, catalysed by receptor tyrosine kinases and receptor tyrosine phosphatases, plays an essential part in cell signaling during axonal development. The receptor protein tyrosine phosphatase PTPσ has been implicated in the growth, guidance and repair of axons from retinal axons. This phosphatase has also been implicated in motor axon growth and innervation. Insect orthologues of PTPσ are also implicated in the recognition of muscle target cells. A potential extracellular ligand for vertebrate PTPσ has been previously localised in developing skeletal muscle. The identity of this muscle ligand is currently unknown, but is appears unrelated to the heparan sulphate ligands of PTPσ. In this study, we have used affinity chromatography and tandem mass spectrometry to identify nucleolin as a binding partner for PTPσ in skeletal muscle tissue. Nucleolin, both from tissue lysates and in purified form, binds to PTPσ ectodomains. Its expression pattern overlaps with that of the PTPσ-binding partner previously localised in muscle and we demonstrate that a significant amount of muscle-associated nucleolin is present on the cell surface of developing myotubes. Furthermore, two nucleolin-binding components, lactoferrin and the HB-19 peptide, can block the interaction of PTPσ probes with muscle in tissue sections. These data suggest that cell surface-associated nucleolin is a potential component of the muscle binding sites for PTPσ, and would be accessible on the cell surface to axonal PTPσ.
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