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 language | English (US) |
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Pages (from-to) | 388-399 |
Number of pages | 12 |
Journal | Experimental Cell Research |
Volume | 303 |
Issue number | 2 |
DOIs | |
State | Published - Feb 15 2005 |
Keywords
- Localization
- Nesprin-1
- Nuclear envelope
- PDE4D3
- Ryanodine receptor
- Spectrin repeat
- Targeting
- mAKAP
ASJC Scopus subject areas
- Cell Biology