Mutually exclusive binding of PP1 and RNA to AKAP149 affects the mitochondrial network.
نویسندگان
چکیده
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.
منابع مشابه
Recruitment of Protein Phosphatase 1 to the Nuclear Envelope by a-Kinase Anchoring Protein Akap149 Is a Prerequisite for Nuclear Lamina Assembly
Subcellular targeting of cAMP-dependent protein kinase (protein kinase A [PKA]) and of type 1 protein phosphatase (PP1) is believed to enhance the specificity of these enzymes. We report that in addition to anchoring PKA, A-kinase anchoring protein AKAP149 recruits PP1 at the nuclear envelope (NE) upon somatic nuclear reformation in vitro, and that PP1 targeting to the NE is a prerequisite for ...
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Reassembly of the nuclear envelope (NE) at the end of mitosis requires targeting of the B-type lamin protein phosphatase, PP1, to the envelope by A-kinase anchoring protein AKAP149. We show here that NE-associated AKAP149 is a novel PP1-specifying subunit involved in maintaining nuclear architecture through G1 phase. PP1 remains associated with NE-bound AKAP149 during G1 but is released from AK...
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We previously showed that targeting of protein phosphatase 1 (PP1) to the nuclear envelope (NE) by the A-kinase anchoring protein, AKAP149, correlates with nuclear assembly of B-type lamins in vitro. We demonstrate here that failure of AKAP149-mediated assembly of B-type lamins into the nuclear lamina at the end of mitosis is followed by apoptosis, and induces expression of the gene encoding A-...
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We previously showed that targeting of protein phosphatase 1 (PP1) to the nuclear envelope (NE) by the A-kinase anchoring protein, AKAP149, correlates with nuclear assembly of B-type lamins in vitro. We demonstrate here that failure of AKAP149-mediated assembly of B-type lamins into the nuclear lamina at the end of mitosis is followed by apoptosis, and induces expression of the gene encoding A-...
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A-kinase-anchoring protein 149 (AKAP149) is a member of a structurally diverse, though functionally similar anchoring protein family and is localized to the outer membrane of mitochondria and in the endoplasmic reticulum-nuclear envelope network. AKAP149 plays an important role in controlling the subcellular localization and temporal specificity of protein phosphorylation and mRNA metabolism by...
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ورودعنوان ژورنال:
- Human molecular genetics
دوره 18 5 شماره
صفحات -
تاریخ انتشار 2009