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Hum Mol Genet. 2009 Mar 1;18(5):978-87. doi: 10.1093/hmg/ddn425. Epub 2008 Dec 12.

Mutually exclusive binding of PP1 and RNA to AKAP149 affects the mitochondrial network.

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  • 11Institute of Basic Medical Sciences, Department of Biochemistry, University of Oslo, Post Box 1112, Blindern, 0317 Oslo, Norway.


A-kinase-anchoring protein 149 (AKAP149) is a membrane protein of the mitochondrial and endoplasmic reticulum/nuclear envelope network. AKAP149 controls the subcellular localization and temporal order of protein phosphorylation by tethering protein kinases and phosphatases to these compartments. AKAP149 also includes an RNA-binding K homology (KH) domain, the loss of function of which has been associated in other proteins with neurodegenerative syndromes. We show here that protein phosphatase 1 (PP1) binding occurs through a conserved RVXF motif found in the KH domain of AKAP149 and that PP1 and RNA binding to this same site is mutually exclusive and controlled through a novel, phosphorylation-dependent mechanism. A collapse of the mitochondrial network is observed upon introduction of RNA-binding deficient mutants of AKAP149, pointing to the importance of RNA tethering to the mitochondrial membrane by AKAP149 for mitochondrial distribution.

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