Sajnani-Perez Gustavo, Chilton John K, Aricescu A Radu, Haj Fawaz, Stoker Andrew W
Neural Development Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK.
Mol Cell Neurosci. 2003 Jan;22(1):37-48. doi: 10.1016/s1044-7431(02)00026-x.
PTPsigma is a receptor tyrosine phosphatase that is expressed widely in the developing nervous system and that controls the growth and retinotopic mapping of retinal axons. PTPsigma is also expressed in motor neurons where its function is unclear. Given that invertebrate relatives of PTPsigma can control motor axon guidance, target contact, and synaptogenesis, we have asked if extracellular ligands exist for cPTPsigma, the avian PTPsigma orthologue, in the neuromuscular system. Of the two major isoforms cPTPsigma1 and cPTPsigma2, only the shorter cPTPsigma1 isoform is expressed in developing spinal motor neurons and their axons. We show that ectodomains of cPTPsigma1, but not of cPTPsigma2, bind specifically to developing skeletal myotubes. The putative myotube ligand is not related to the previously described binding of cPTPsigma to heparan sulfates within the proteoglycans agrin and collagen XVIII, since heparinase treatment of myotubes does not alter cPTPsigma1 binding and since most mutations that abolish binding of cPTPsigma1 to heparin do not affect myotube binding. The expression of cPTPsigma1 in motor axons and its direct binding to target myotubes suggest an isoform-specific role for axonally expressed cPTPsigma1 during establishment or maintenance of neuromuscular contacts.
PTPsigma是一种受体酪氨酸磷酸酶，在发育中的神经系统中广泛表达，控制视网膜轴突的生长和视网膜定位映射。PTPsigma在运动神经元中也有表达，但其功能尚不清楚。鉴于PTPsigma的无脊椎动物亲属可以控制运动轴突导向、靶标接触和突触形成，我们不禁要问，在神经肌肉系统中，鸟类PTPsigma直系同源物cPTPsigma是否存在细胞外配体。在两种主要的异构体cPTPsigma1和cPTPsigma2中，只有较短的cPTPsigma1异构体在发育中的脊髓运动神经元及其轴突中表达。我们发现，cPTPsigma1的胞外结构域而非cPTPsigma2的胞外结构域能特异性结合发育中的骨骼肌肌管。假定的肌管配体与先前描述的cPTPsigma与蛋白聚糖聚集蛋白和XVIII型胶原中的硫酸乙酰肝素结合无关，因为用肝素酶处理肌管不会改变cPTPsigma1的结合，而且大多数消除cPTPsigma1与肝素结合的突变并不影响与肌管的结合。cPTPsigma1在运动轴突中的表达及其与靶标肌管的直接结合表明，轴突表达的cPTPsigma1在神经肌肉接触的建立或维持过程中具有异构体特异性作用。
