%0 Journal Article
%T The function of Shp2 tyrosine phosphatase in the dispersal of acetylcholine receptor clusters
%A Yueping K Qian
%A Ariel WS Chan
%A Raghavan Madhavan
%A H Benjamin Peng
%J BMC Neuroscience
%D 2008
%I BioMed Central
%R 10.1186/1471-2202-9-70
%X Using an assay system that allows AChR cluster assembly and disassembly to be studied separately and quantitatively, we describe a previously unrecognized role of the tyrosine phosphatase Shp2 in AChR cluster disassembly. Shp2 was robustly expressed in embryonic Xenopus muscle in vivo and in cultured myotomal muscle cells, and treatment of the muscle cultures with an inhibitor of Shp2 (NSC-87877) blocked the dispersal of pre-patterned AChR clusters by synaptogenic stimuli. In contrast, over-expression in muscle cells of either wild-type or constitutively active Shp2 accelerated cluster dispersal. Significantly, forced expression in muscle of the Shp2-activator SIRP¦Á1 (signal regulatory protein ¦Á1) also enhanced the disassembly of AChR clusters, whereas the expression of a truncated SIRP¦Á1 mutant that suppresses Shp2 signaling inhibited cluster disassembly.Our results suggest that Shp2 activation by synaptogenic stimuli, through signaling intermediates such as SIRP¦Á1, promotes the dispersal of pre-patterned AChR clusters to facilitate the selective accumulation of AChRs at developing NMJs.Synapses facilitate efficient neuronal communication by bringing close together the organelles and molecules involved in the release and detection of neurotransmitters. Thus, to understand how synapses function, it is necessary to elucidate the signaling pathways that regulate the development of cellular specializations unique to synapses. For this purpose, one particular synaptic specialization ¨C found at the vertebrate neuromuscular junction (NMJ) ¨C has been examined extensively over the past several decades. Enriched in the postsynaptic domain of the NMJ are ion channels named acetylcholine (ACh) receptors (AChRs) that open upon binding to the neurotransmitter ACh; opening of AChRs depolarizes the synaptic region of muscle to trigger contraction. The synaptic aggregation of AChRs during NMJ assembly is therefore a process of paramount importance, one that is recognized to be tigh
%U http://www.biomedcentral.com/1471-2202/9/70