L‐type calcium channels mediate acetylcholine receptor aggregation on cultured muscle

Milholland, Rebecca B. R.; Dulla, Chris G.; Gordon, Herman

doi:10.1002/dneu.20397

Cited by 7 publications

(6 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In fact, present results come at a time when novel physiological roles for the corresponding voltagedependent Ca 2+ entry are being proposed: The slow Ca 2+ current was recently postulated to be involved in the aggregation of acetylcholine receptors during postsynaptic development [24] and in the fusion of satellite cells [20]. More interestingly, it is now proposed to play a role in maintaining Ca 2+ transients in response to prolonged depolarisations or repeated trains of action potentials [16].…”

Section: Discussionmentioning

confidence: 89%

Expression of the muscular dystrophy-associated caveolin-3P104L mutant in adult mouse skeletal muscle specifically alters the Ca2+ channel function of the dihydropyridine receptor

Weiss

Couchoux

Legrand

et al. 2008

Pflugers Arch - Eur J Physiol

View full text Add to dashboard Cite

Caveolins are plasma-membrane-associated proteins potentially involved in a variety of signalling pathways. Different mutations in CAV3, the gene encoding for the muscle-specific isoform caveolin-3 (Cav-3), lead to muscle diseases, but the underlying molecular mechanisms remain largely unknown. Here, we explored the functional consequences of a Cav-3 mutation (P104L) inducing the 1C type limb-girdle muscular dystrophy (LGMD 1C) in human on intracellular Ca(2+) regulation of adult skeletal muscle fibres. A YFP-tagged human Cav-3(P104L) mutant was expressed in vivo in muscle fibres from mouse. Western blot analysis revealed that expression of this mutant led to an approximately 80% drop of the level of endogenous Cav-3. The L-type Ca(2+) current density was found largely reduced in fibres expressing the Cav-3(P104L) mutant, with no change in the voltage dependence of activation and inactivation. Interestingly, the maximal density of intramembrane charge movement was unaltered in the Cav-3(P104L)-expressing fibres, suggesting no change in the total amount of functional voltage-sensing dihydropyridine receptors (DHPRs). Also, there was no obvious alteration in the properties of voltage-activated Ca(2+) transients in the Cav-3(P104L)-expressing fibres. Although the actual role of the Ca(2+) channel function of the DHPR is not clearly established in adult skeletal muscle, its specific alteration by the Cav-3(P104L) mutant suggests that it may be involved in the physiopathology of LGMD 1C.

show abstract

Section: Discussionmentioning

confidence: 89%

Expression of the muscular dystrophy-associated caveolin-3P104L mutant in adult mouse skeletal muscle specifically alters the Ca2+ channel function of the dihydropyridine receptor

Weiss

Couchoux

Legrand

et al. 2008

Pflugers Arch - Eur J Physiol

View full text Add to dashboard Cite

show abstract

“…Thus, the two signaling mechanisms possess partially redundant actions on the formation and organization of AChR clusters. Previous cell culture studies showed the importance of Ca V 1.1 and β-catenin for agrin-induced AChR clustering ( Milholland et al., 2007 ; Zhang et al., 2007 ). This is consistent with our data at E14.5, where we see substantially reduced AChR cluster sizes in both single knockouts.…”

Section: Discussionmentioning

confidence: 98%

Counteractive and cooperative actions of muscle β-catenin and CaV1.1 during early neuromuscular synapse formation

Kaplan

Flucher

2022

iScience

View full text Add to dashboard Cite

“…Intriguingly, AChR activity, which favors dispersal in embryonic muscle, stabilizes AChRs during synaptic competition [ 62 ], which could be due to changes in the molecular makeup of AChR subunits or clusters during development [ 18 ]. And, the elevation of intracellular Ca 2+ by agonists of AChRs and L-type calcium channels actually promote AChR clustering [ 63 , 64 ], suggesting that Ca 2+ can either favor AChR cluster assembly and stabilization or cluster destabilization and dispersal (through calpain/Cdk5).…”

Section: Discussionmentioning

confidence: 99%

The function of Shp2 tyrosine phosphatase in the dispersal of acetylcholine receptor clusters

et al. 2008

View full text Add to dashboard Cite

BackgroundA crucial event in the development of the vertebrate neuromuscular junction (NMJ) is the postsynaptic enrichment of muscle acetylcholine (ACh) receptors (AChRs). This process involves two distinct steps: the local clustering of AChRs at synapses, which depends on the activation of the muscle-specific receptor tyrosine kinase MuSK by neural agrin, and the global dispersal of aneural or "pre-patterned" AChR aggregates, which is triggered by ACh or by synaptogenic stimuli. We and others have previously shown that tyrosine phosphatases, such as the SH2 domain-containing phosphatase Shp2, regulate AChR cluster formation in muscle cells, and that tyrosine phosphatases also mediate the dispersal of pre-patterned AChR clusters by synaptogenic stimuli, although the specific phosphatases involved in this latter step remain unknown.ResultsUsing 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 SIRPα1 (signal regulatory protein α1) also enhanced the disassembly of AChR clusters, whereas the expression of a truncated SIRPα1 mutant that suppresses Shp2 signaling inhibited cluster disassembly.ConclusionOur results suggest that Shp2 activation by synaptogenic stimuli, through signaling intermediates such as SIRPα1, promotes the dispersal of pre-patterned AChR clusters to facilitate the selective accumulation of AChRs at developing NMJs.

show abstract

L‐type calcium channels mediate acetylcholine receptor aggregation on cultured muscle

Cited by 7 publications

References 54 publications

Expression of the muscular dystrophy-associated caveolin-3P104L mutant in adult mouse skeletal muscle specifically alters the Ca2+ channel function of the dihydropyridine receptor

Expression of the muscular dystrophy-associated caveolin-3P104L mutant in adult mouse skeletal muscle specifically alters the Ca2+ channel function of the dihydropyridine receptor

Counteractive and cooperative actions of muscle β-catenin and CaV1.1 during early neuromuscular synapse formation

The function of Shp2 tyrosine phosphatase in the dispersal of acetylcholine receptor clusters

Contact Info

Product

Resources

About