title: Microtubule-dependent association of AKAP350A and CCAR1 with RNA stress granules.
abstract: Recent investigations have highlighted the importance of subcellular localization of mRNAs to cell function. While AKAP350A, a multifunctional scaffolding protein, localizes to the Golgi apparatus and centrosomes, we have now identified a cytosolic pool of AKAP350A. Analysis of AKAP350A scaffolded complexes revealed two novel interacting proteins, CCAR1 and caprin-1. CCAR1, caprin-1 and AKAP350A along with G3BP, a stress granule marker, relocate to RNA stress granules after arsenite treatment. Stress also caused loss of AKAP350 from the Golgi and fragmentation of the Golgi apparatus. Disruption of microtubules with nocodazole altered stress granule formation and changed their morphology by preventing fusion of stress granules. In the presence of nocodazole, arsenite induced smaller granules with the vast majority of AKAP350A and CCAR1 separated from G3BP-containing granules. Similar to nocodazole treatment, reduction of AKAP350A or CCAR1 expression also altered the size and number of G3BP-containing stress granules induced by arsenite treatment. A limited set of 69 mRNA transcripts was immunoisolated with AKAP350A even in the absence of stress, suggesting the association of AKAP350A with mRNA transcripts. These results provide the first evidence for the microtubule dependent association of AKAP350A and CCAR1 with RNA stress granules.
authors.affiliation: Department of Surgery Vanderbilt University School of Medicine Nashville, TN 37232-2733, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Kolobova
authors.forename: Andrey
authors.initials: A
authors.lastname: Efimov
authors.forename: Irina
authors.initials: I
authors.lastname: Kaverina
authors.forename: Arun K
authors.initials: AK
authors.lastname: Rishi
authors.forename: John W
authors.initials: JW
authors.lastname: Schrader
authors.forename: Amy-Joan
authors.initials: AJ
authors.lastname: Ham
authors.forename: M Cecilia
authors.initials: MC
authors.lastname: Larocca
authors.forename: James R
authors.initials: JR
authors.lastname: Goldenring
mesh_terms: D054758:A Kinase Anchor Proteins / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D018053:Arsenites / Q000494:pharmacology; D002352:Carrier Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004265:DNA Helicases; D006056:Golgi Apparatus / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008870:Microtubules / Q000378:metabolism*; D015739:Nocodazole / Q000494:pharmacology; D000075223:Poly-ADP-Ribose Binding Proteins; D021381:Protein Transport; D020365:RNA Helicases; D000067776:RNA Recognition Motif Proteins; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*
chemical_list: D054758:A Kinase Anchor Proteins; C119719:AKAP9 protein, human; D051017:Apoptosis Regulatory Proteins; D018053:Arsenites; C486562:CAPRIN1 protein, human; C477529:CCAR1 protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D000067776:RNA Recognition Motif Proteins; D012333:RNA, Messenger; D004265:DNA Helicases; C116070:G3BP1 protein, human; D020365:RNA Helicases; C015001:arsenite; D015739:Nocodazole