一氧化氮合酶与由PDZ结构域介导的突触后致密蛋白PSD-95和α1-肌营养不良素的相互作用。

Interaction of nitric oxide synthase with the postsynaptic density protein PSD-95 and alpha1-syntrophin mediated by PDZ domains.

作者信息

Brenman J E, Chao D S, Gee S H, McGee A W, Craven S E, Santillano D R, Wu Z, Huang F, Xia H, Peters M F, Froehner S C, Bredt D S

机构信息

Department of Physiology, School of Medicine, University of California at San Fancisco, California 94143, USA.

出版信息

Cell. 1996 Mar 8;84(5):757-67. doi: 10.1016/s0092-8674(00)81053-3.

DOI:10.1016/s0092-8674(00)81053-3

PMID:8625413

Abstract

Neuronal nitric oxide synthase (nNOS) is concentrated at synaptic junctions in brain and motor endplates in skeletal muscle. Here, we show that the N-terminus of nNOS, which contains a PDZ protein motif, interacts with similar motifs in postsynaptic density-95 protein (PSD-95) and a related novel protein, PSD-93.nNOS and PSD-95 are coexpressed in numerous neuronal populations, and a PSD-95/nNOS complex occurs in cerebellum. PDZ domain interactions also mediate binding of nNOS to skeletal muscle syntrophin, a dystrophin-associated protein. nNOS isoforms lacking a PDZ domain, identified in nNOSdelta/delta mutant mice, do not associate with PSD-95 in brain or with skeletal muscle sarcolemma. Interaction of PDZ-containing domains therefore mediates synaptic association of nNOS and may play a more general role in formation of macromolecular signaling complexes.

摘要

神经元型一氧化氮合酶（nNOS）集中于脑内的突触连接处以及骨骼肌的运动终板。在此，我们表明，含有PDZ蛋白基序的nNOS的N端，可与突触后致密蛋白95（PSD - 95）以及一种相关的新蛋白PSD - 93中的类似基序相互作用。nNOS和PSD - 95在众多神经元群体中共表达，并且在小脑中存在PSD - 95/nNOS复合物。PDZ结构域相互作用还介导nNOS与骨骼肌肌养蛋白（一种与肌营养不良蛋白相关的蛋白）的结合。在nNOSδ/δ突变小鼠中鉴定出的缺乏PDZ结构域的nNOS亚型，在脑中不与PSD - 95结合，在骨骼肌肌膜中也不结合。因此，含PDZ结构域的相互作用介导了nNOS的突触结合，并且可能在大分子信号复合物的形成中发挥更广泛的作用。