Protein kinase A (PKA) and the nuclear A-kinase–anchoring protein AKAP95 have previously been shown to localize in separate compartments in interphase but associate at mitosis. We demonstrate here a role for the mitotic AKAP95–PKA complex. In HeLa cells, AKAP95 is associated with the nuclear matrix in interphase and redistributes mostly into a chromatin fraction at mitosis. In a cytosolic extract derived from mitotic cells, AKAP95 recruits the RIIα regulatory subunit of PKA onto chromatin. Intranuclear immunoblocking of AKAP95 inhibits chromosome condensation at mitosis and in mitotic extract in a PKA-independent manner. Immunodepletion of AKAP95 from the extract or immunoblocking of AKAP95 at metaphase induces premature chromatin decondensation. Condensation is restored in vitro by a recombinant AKAP95 fragment comprising the 306–carboxy-terminal amino acids of the protein. Maintenance of condensed chromatin requires PKA binding to chromatin-associated AKAP95 and cAMP signaling through PKA. Chromatin-associated AKAP95 interacts with Eg7, the human homologue of Xenopus pEg7, a component of the 13S condensin complex. Moreover, immunoblocking nuclear AKAP95 inhibits the recruitment of Eg7 to chromatin in vitro. We propose that AKAP95 is a multivalent molecule that in addition to anchoring a cAMP/PKA–signaling complex onto chromosomes, plays a role in regulating chromosome structure at mitosis.
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13 December 1999
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December 13 1999
The a-Kinase–Anchoring Protein Akap95 Is a Multivalent Protein with a Key Role in Chromatin Condensation at Mitosis
Philippe Collas,
Philippe Collas
aInstitute of Medical Biochemistry, Faculty of Medicine, University of Oslo, Blindern, 0317 Oslo, Norway
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Katherine Le Guellec,
Katherine Le Guellec
bCentre National Recherche Scientifique UPR41, Biologie et Génétique du Dévelopement, Faculté de Médecine, 35043 Rennes Cedex, France
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Kjetil Taskén
Kjetil Taskén
aInstitute of Medical Biochemistry, Faculty of Medicine, University of Oslo, Blindern, 0317 Oslo, Norway
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Philippe Collas
aInstitute of Medical Biochemistry, Faculty of Medicine, University of Oslo, Blindern, 0317 Oslo, Norway
Katherine Le Guellec
bCentre National Recherche Scientifique UPR41, Biologie et Génétique du Dévelopement, Faculté de Médecine, 35043 Rennes Cedex, France
Kjetil Taskén
aInstitute of Medical Biochemistry, Faculty of Medicine, University of Oslo, Blindern, 0317 Oslo, Norway
Abbreviations used in this paper: AKAP, A-kinase–anchoring protein; CDK1, cyclin-dependent kinase 1; LBR, lamin B receptor; PCD, premature chromatin decondensation; PKA, protein kinase A; R and C, regulatory and catalytic subunit of PKA, respectively; SMC, structural maintenance of chromosome.
Received:
August 27 1999
Revision Requested:
October 18 1999
Accepted:
November 03 1999
Online ISSN: 1540-8140
Print ISSN: 0021-9525
© 1999 The Rockefeller University Press
1999
The Rockefeller University Press
J Cell Biol (1999) 147 (6): 1167–1180.
Article history
Received:
August 27 1999
Revision Requested:
October 18 1999
Accepted:
November 03 1999
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Citation
Philippe Collas, Katherine Le Guellec, Kjetil Taskén; The a-Kinase–Anchoring Protein Akap95 Is a Multivalent Protein with a Key Role in Chromatin Condensation at Mitosis. J Cell Biol 13 December 1999; 147 (6): 1167–1180. doi: https://doi.org/10.1083/jcb.147.6.1167
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