Regulation of tyrosine phosphorylation of the nicotinic acetylcholine receptor at the rat neuromuscular lunction

Qu, Zhican; Moritz, Elizabeth; Huganir, Richard L.

doi:10.1016/0896-6273(90)90049-l

Cited by 132 publications

(86 citation statements)

References 34 publications

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“…NG108-15 cells form functional cholinergic synapses on myotubes (Christian et al, 1977), and a factor from these cells promotes nAChR clustering (Christian et al, 1978). Coculture of myotubes with NG108-15 cells increases nAChR ␤ subunit tyrosine phosphorylation (K. Miles, unpublished observations), a phosphorylation pattern shared by mature nAChRs in the neuromuscular junction (Qu et al, 1990). NG108-15 cell coculture with myotubes may mimic other events that occur during synaptogenesis at the neuromuscular junction.…”

Section: Discussionmentioning

confidence: 99%

Neural Influence on Protein Kinase C Isoform Expression in Skeletal Muscle

et al. 1996

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Protein kinase C (PKC) is a family of enzymes involved in synapse formation and signal transduction at the neuromuscular junction. Two PKC isoforms, classical PKC ␣ and novel PKC , have been shown to be enriched in skeletal muscle or localized to the endplate. We examined the role of nerve in regulating the expression of these PKC isoforms in rat skeletal muscle by denervating diaphragm muscle and measuring PKC protein expression at various postoperative times. nPKC protein levels decreased 65% after denervation, whereas cPKC ␣ levels increased 80% compared with control hemidiaphragms. These results suggest that innervation regulates PKC and ␣ isoform expression in skeletal muscle. To explore further how nerve regulates PKC expression, we characterized PKC isoform expression in rat myotubes deprived of neural input. Myoblast expression of nPKC was low, and the increase in nPKC expression that occurred during differentiation into myotubes resulted in levels of nPKC significantly below adult skeletal muscle. cPKC ␣ expression in myoblasts increased during differentiation to levels that exceeded expression in adult skeletal muscle. Coculturing myotubes with a neuroblastoma X glioma hybrid clonal cell line (NG108-15) increased nPKC expression, but not cPKC ␣, suggesting that nPKC in skeletal muscle and myotubes is regulated by nerve contact or by a factor(s) provided by nerve. Treating myotubes with tetrodotoxin did not affect either basal-or NG108-15 cell-stimulated nPKC expression. Together these results suggest that expression of nPKC in skeletal muscle is regulated by a transynaptic interaction with nerve that specifically influences nPKC expression.

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Section: Discussionmentioning

confidence: 99%

Neural Influence on Protein Kinase C Isoform Expression in Skeletal Muscle

et al. 1996

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“…All these observations suggest that protein phosphorylation is involved in the signal transduction for cell activation and proliferation. In addition, tyrosine phosphorylation was demonstrated to be modulated during the development of the central nervous system [29]. To analyze the mechanisms of regulation during differentiation from the perspective of PTPs, we have recently cloned and characterized a mouse type II RPTP, named MPTP~.…”

Section: Introductionmentioning

confidence: 99%

Developmental regulation of gene expression for the MPTPδ isoforms in the central nervous system and the immune system

Mizuno¹,

Hasegawa²,

Ogimoto³

et al. 1994

FEBS Letters

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MPTP6 is a murine transmembrane protein tyrosine phosphatase which has three isoforms, types A-C, differing in the structure of the extracellular regions. In this study, we examined MPTP~ isoform expression in the brain and the immune system at discrete developmental or differentiation stages. RT-PCR analysis demonstrated that another isoform, type D, is transcribed from the MPTP~ gene. In\the brain, only type D was expressed until postnatal day 7 (P7), but after P14, all four isoforms were detected. In contrast, the spleen, thymus and all the hematopoietic cell lines examined express only types B and C isoforms. An in situ hybridization study showed that MPTP6 mRNA is diffusely expressed throughout the spleen, but its expression in the thymus is restricted to the medullary region.

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“…Phosphorylation of the AChR by both serine and tyrosine kinases is associated with an increased rate of receptor desensitization (Huganir et al, 1986;Hopfield et al, 1988). In addition, agrin-induced tyrosine phosphorylation of the AChR may play a role in its clustering to high densities in the postsynaptic membrane of the neuromuscular junction (Qu et al, 1990;Wallace et al, 1991;Qu and Huganir, 1994;Wallace, 1994;Ferns et al, 1996).…”

mentioning

confidence: 99%

“…The identification of ion channels, including potassium channels (Lev et al, 1995;Holmes et al, 1996), NMDA receptors (Moon et al, 1994;Wang and Salter, 1994;Lau and Huganir, 1995), and nicotinic acetylcholine receptors (AChRs) (Huganir et al, 1984;Qu et al, 1990), as substrates for tyrosine kinases suggests that this modification may play an important role in the regulation of synaptic function throughout the nervous system. The bulk of our knowledge about the functional consequences of tyrosine phosphorylation of ion channels comes from studies of the AChR at the neuromuscular junction (NMJ) and its homologous synapse in the electric organ of Torpedo.…”

mentioning

confidence: 99%

Tyrosine Phosphorylation of Nicotinic Acetylcholine Receptor Mediates Grb2 Binding

Colledge

Froehner

1997

J. Neurosci.

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Tyrosine phosphorylation of the nicotinic acetylcholine receptor (AChR) is associated with an altered rate of receptor desensitization and also may play a role in agrin-induced receptor clustering. We have demonstrated a previously unsuspected interaction between Torpedo AChR and the adaptor protein Grb2. The binding is mediated by the Src homology 2 (SH2) domain of Grb2 and the tyrosine-phosphorylated ␦ subunit of the AChR. Dephosphorylation of the ␦ subunit abolishes Grb2 binding. A cytoplasmic domain of the ␦ subunit contains a binding motif (pYXNX) for the SH2 domain of Grb2. Indeed, a phosphopeptide corresponding to this region of the ␦ subunit binds to Grb2 SH2 fusion proteins with relatively high affinity, whereas a peptide lacking phosphorylation on tyrosine exhibits no binding. Grb2 is colocalized with the AChR on the innervated face of Torpedo electrocytes. Furthermore, Grb2 specifically copurifies with AChR solubilized from postsynaptic membranes. These data suggest a novel role for tyrosine phosphorylation of the AChR in the initiation of a Grb2-mediated signaling cascade at the postsynaptic membrane.

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Regulation of tyrosine phosphorylation of the nicotinic acetylcholine receptor at the rat neuromuscular lunction

Cited by 132 publications

References 34 publications

Neural Influence on Protein Kinase C Isoform Expression in Skeletal Muscle

Neural Influence on Protein Kinase C Isoform Expression in Skeletal Muscle

Developmental regulation of gene expression for the MPTPδ isoforms in the central nervous system and the immune system

Tyrosine Phosphorylation of Nicotinic Acetylcholine Receptor Mediates Grb2 Binding

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