Nesprin-1α contributes to the targeting of mAKAP to the cardiac myocyte nuclear envelope

Genevieve C. Pare, Juliet L. Easlick, John M. Mislow, Elizabeth M. McNally, Michael S. Kapiloff

Research output: Contribution to journalArticle

77 Scopus citations

Abstract

Muscle A-kinase anchoring protein (mAKAP) is a scaffold protein found principally at the nuclear envelope of striated myocytes. mAKAP maintains a complex consisting of multiple signal transduction molecules including the cAMP-dependent protein kinase A, the ryanodine receptor calcium release channel, phosphodiesterase type 4D3, and protein phosphatase 2A. By an unknown mechanism, a domain containing spectrin repeats is responsible for targeting mAKAP to the nuclear envelope. We now demonstrate that the integral membrane protein nesprin-1α serves as a receptor for mAKAP on the nuclear envelope in cardiac myocytes. Nesprin-1α is inserted into the nuclear envelope by a conserved, C-terminal, klarsicht-related transmembrane domain and forms homodimers by the binding of an amino-terminal spectrin repeat domain. Through the direct binding of the nesprin-1α amino-terminal dimerization domain to the third mAKAP spectrin repeat, nesprin-1α targets mAKAP to the nuclear envelope. In turn, overexpression of these spectrin repeat domains in myocytes can displace mAKAP from nesprin-1α.

Original languageEnglish (US)
Pages (from-to)388-399
Number of pages12
JournalExperimental Cell Research
Volume303
Issue number2
DOIs
StatePublished - Feb 15 2005

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Keywords

  • Localization
  • mAKAP
  • Nesprin-1
  • Nuclear envelope
  • PDE4D3
  • Ryanodine receptor
  • Spectrin repeat
  • Targeting

ASJC Scopus subject areas

  • Cell Biology

Cite this

Pare, G. C., Easlick, J. L., Mislow, J. M., McNally, E. M., & Kapiloff, M. S. (2005). Nesprin-1α contributes to the targeting of mAKAP to the cardiac myocyte nuclear envelope. Experimental Cell Research, 303(2), 388-399. https://doi.org/10.1016/j.yexcr.2004.10.009