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Just in time and place: NOS/NO system assembly in neuromuscular junction formation
Author(s) -
Blottner Dieter,
Lück Gabriele
Publication year - 2001
Publication title -
microscopy research and technique
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.536
H-Index - 118
eISSN - 1097-0029
pISSN - 1059-910X
DOI - 10.1002/jemt.1168
Subject(s) - agrin , postsynaptic potential , neuromuscular junction , microbiology and biotechnology , biology , acetylcholine receptor , postsynaptic density , signal transduction , palmitoylation , neuroscience , biochemistry , receptor , cysteine , enzyme
Recent advances in the molecular, biochemical, and anatomical aspects of postsynaptic membrane components at the neuromuscular junction (NMJ) are briefly reviewed focussing on assembly, architecture, and function of the multi‐subunit dystrophin‐protein complex (DPC) and its associated nitric oxide (NO)‐signaling complex. Elucidation of unique structural binding motifs of NO‐synthases (NOS), and microscopical codistribution of neuronal NOS (nNOS), the major isoform of NOS expressed at the NMJ, with known synaptic proteins, i.e., family members of the DPC, nicotinic acetylcholine receptor (AChR), NMDA‐receptor, type‐1 sodium and Shaker K + ‐channel proteins, and linker proteins (e.g., PSD‐95, 43K‐rapsyn), suggests targeting and assembly of the NO‐signaling pathway at postsynaptic membrane components. NO mediates agrin‐induced AChR‐aggregation and downstream signal transduction in C2 skeletal myotubes while administration of L‐arginine, the limiting substrate for NO‐biosynthesis, enhances aggregation of synapse‐specific components such as utrophin. At the NMJ, NO appears to be a mediator of (1) early synaptic protein clustering, (2) synaptic receptor activity and transmitter release, or (3) downstream signaling for transcriptional control. Multidisciplinary data obtained from cellular and molecular studies and from immunolocalization investigations have led us to propose a working model for step‐by‐step binding of nNOS, e.g., to subunit domains of targeted and/or preexisting membrane components. Formation of NOS‐membrane complexes appears to be governed by agrin‐signaling as well as by NO‐signaling, supporting the idea that parallel signaling pathways may account for the spatiotemporally defined postsynaptic assembly thereby linking the NOS/NO‐signaling cascade to early membrane aggregations and at the right places nearby preexisting targets (e.g., juxtaposition of NO source and target) in synapse formation. Microsc. Res. Tech. 55:171–180, 2001. © 2001 Wiley‐Liss, Inc.