A Novel Receptor for Myelin associated Glycoprotein

描述（由申请人提供）：受损的中枢神经系统（CNS）轴突的再生能力差主要是由于与CNS髓磷脂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神经突生长。我已经鉴定了Nogo受体（NgR1）同源物NgR2作为MAG的新型和高亲和力结合伴侣。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反应性。所提出的实验旨在解决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物化学程序来询问NgR1和NgR2是否使用保守的机制来发出生长抑制信号。将进行NgR2功能丧失研究以检查NgR2是否是体外原代神经元中MAG抑制所必需的。预计这些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.