Mutually exclusive binding of PP1 and RNA to AKAP149 affects the mitochondrial network.
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.
Rogne
Marie
M
1Institute of Basic Medical Sciences, Department of Biochemistry, University of Oslo, Post Box 1112, Blindern, 0317 Oslo, Norway.
Stokka
Anne Jorunn
AJ
Taskén
Kjetil
K
Collas
Philippe
P
Küntziger
Thomas
T
D054758:A Kinase Anchor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D010766:Phosphorylation; D011485:Protein Binding; D054645:Protein Phosphatase 1 / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D054758:A Kinase Anchor Proteins; C105137:AKAP1 protein, human; D016601:RNA-Binding Proteins; D054645:Protein Phosphatase 1