A Novel Receptor for Myelin associated Glycoprotein

描述(申请人提供)：受损的中枢神经系统(CNS)轴突再生能力差的主要原因是与中枢神经系统髓鞘相关的生长抑制蛋白。髓鞘相关糖蛋白(MAG)是一种唾液酸结合凝集素，以神经氨酸酶敏感的方式抑制轴突生长。我已经确定Nogo受体(NgR1)同源物NgR2是MAG的一个新的高亲和力结合伙伴。NgR2以神经氨酸酶敏感的方式支持MAG结合，并且NgR2的异位表达足以赋予通常不被MAG抑制的神经元MAG反应。这些实验旨在探讨NgR2是否是MAG抑制所必需的，确定NgR1和NgR2之间的功能关系，以及NgR2的作用机制。我将使用组织化学和生化程序来询问NgR1和NgR2是否使用保守的机制来发出抑制生长的信号。将进行NgR2功能丧失研究，以确定NgR2是否是体外培养的原代神经元MAG抑制所必需的。预计所提出的研究将进一步加深我们对MAG用于将生长抑制传递给再生神经元的分子机制的理解。

DESCRIPTION (provided by applicant): The poor regenerative capacity of injured central nervous system (CNS) axons is largely due to growth inhibitory proteins associated with CNS myelin. Myelin-associated glycoprotein (MAG), a sialic acid binding lectin, inhibits neurite outgrowth in a neuraminidase sensitive manner. I have identified the Nogo Receptor (NgR1) homologue NgR2 as a novel and high affinity binding-partner for MAG. NgR2 supports MAG binding in a neuraminidase sensitive manner and ectopic expression of NgR2 is sufficient to confer MAG responsiveness upon neurons normally not inhibited by MAG. The experiments proposed are aimed at addressing whether NgR2 is necessary for MAG inhibition, determine the functional relationship between NgR1 and NgR2, and the NgR2 mechanism of action. I will use histochemical and biochemical procedures to ask whether NgR1 and NgR2 use conserved mechanisms to signal growth inhibition. NgR2 loss-of-function studies will be performed to examine whether NgR2 is necessary for MAG inhibition in primary neurons in vitro. It is anticipated that the studies proposed will further our understanding of the molecular mechanisms used by MAG to communicate growth inhibition to regenerating neurons.