Cell-surface MuSK self-association

A crucial role for the putative signal sequence

Michael J. Bianchetta, Rebecca Betensky, Jonathan B. Cohen

Research output: Contribution to journalArticle

Abstract

The receptor tyrosine kinase MuSK plays a crucial role-both as a signaling molecule and structurally-in the process of clustering nicotinic acetylcholine receptors at the neuromuscular junction. Immunofluorescence microscopy of transiently transfected fibroblasts has been used to visualize the cell-surface distribution of MuSK, which is found in discrete, punctate clusters. This distribution does not result from targeting of MuSK to identified plasma membrane subdomains, and MuSK's association with itself is specific, as MuSK clusters at the cell surface are segregated from clusters of other cotransfected receptor tyrosine kinases. A mutational analysis, using coexpressed pairs of MuSK mutants and chimeras, demonstrates that the putative signal peptide is both necessary and sufficient for association with MuSK. Removal of the intracellular domain or most of the extracellular domain, or replacement of the transmembrane domain, does not abolish MuSK self-association. The N-terminus of the MuSK protein, however, is sufficient to recruit another receptor tyrosine kinase to MuSK clusters. Quantitation and statistical analysis of the amount of colocalization between coexpressed MuSK mutants and chimeras confirm these results.

Original languageEnglish (US)
Pages (from-to)16229-16238
Number of pages10
JournalBiochemistry
Volume44
Issue number49
DOIs
StatePublished - Dec 13 2005

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Receptor Protein-Tyrosine Kinases
Protein Sorting Signals
Neuromuscular Junction
Nicotinic Receptors
Fibroblasts
Cell membranes
Fluorescence Microscopy
Cluster Analysis
Statistical methods
Microscopic examination
Cell Membrane
Molecules
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

Cell-surface MuSK self-association : A crucial role for the putative signal sequence. / Bianchetta, Michael J.; Betensky, Rebecca; Cohen, Jonathan B.

In: Biochemistry, Vol. 44, No. 49, 13.12.2005, p. 16229-16238.

Research output: Contribution to journalArticle

Bianchetta, MJ, Betensky, R & Cohen, JB 2005, 'Cell-surface MuSK self-association: A crucial role for the putative signal sequence', Biochemistry, vol. 44, no. 49, pp. 16229-16238. https://doi.org/10.1021/bi051549j
Bianchetta, Michael J. ; Betensky, Rebecca ; Cohen, Jonathan B. / Cell-surface MuSK self-association : A crucial role for the putative signal sequence. In: Biochemistry. 2005 ; Vol. 44, No. 49. pp. 16229-16238.
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