NCAM 180 acting via a conserved C-terminal domain and MLCK is essential for effective transmission with repetitive stimulation

Luis Polo-Parada, Florian Plattner, Christian Bose, Lynn T. Landmesser

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

NCAM 180 isoform null neuromuscular junctions are unable to effectively mobilize and exocytose synaptic vesicles and thus exhibit periods of total transmission failure during high-frequency repetitive stimulation. We have identified a highly conserved C-terminal (KENESKA) domain on NCAM that is required to maintain effective transmission and demonstrate that it acts via a pathway involving MLCK and probably myosin light chain (MLC) and myosin II. By perfecting a method of introducing peptides into adult NMJs, we tested the hypothesized role of proteins in this pathway by competitive disruption of protein-protein interactions. The effects of KENESKA and other peptides on MLCK and MLC activation and on failures in both wild-type and NCAM 180 null junctions supported this pathway, and serine phosphorylation of KENESKA was critical. We propose that this pathway is required to replenish synaptic vesicles utilized during high levels of exocytosis by facilitating myosin-driven delivery of synaptic vesicles to active zones or their subsequent exocytosis.

Original languageEnglish (US)
Pages (from-to)917-931
Number of pages15
JournalNeuron
Volume46
Issue number6
DOIs
StatePublished - Jun 16 2005

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Neural Cell Adhesion Molecules
Synaptic Vesicles
Myosin Light Chains
Exocytosis
Myosin Type II
Proteins
Neuromuscular Junction
Myosins
Serine
Protein Isoforms
Phosphorylation
Peptides

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

NCAM 180 acting via a conserved C-terminal domain and MLCK is essential for effective transmission with repetitive stimulation. / Polo-Parada, Luis; Plattner, Florian; Bose, Christian; Landmesser, Lynn T.

In: Neuron, Vol. 46, No. 6, 16.06.2005, p. 917-931.

Research output: Contribution to journalArticle

Polo-Parada, Luis ; Plattner, Florian ; Bose, Christian ; Landmesser, Lynn T. / NCAM 180 acting via a conserved C-terminal domain and MLCK is essential for effective transmission with repetitive stimulation. In: Neuron. 2005 ; Vol. 46, No. 6. pp. 917-931.
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