Original Article

The A-kinase–Anchoring Protein AKAP95 Is a Multivalent Protein with a Key Role in Chromatin Condensation at Mitosis

Correspondence to: Philippe Collas, Institute of Medical Biochemistry, Faculty of Medicine, University of Oslo, P.O. Box 1112 Blindern, 0317 Oslo, Norway. Tel:47-22-85-10-13 Fax:47-22-85-14-97 E-mail:philippe.collas{at}basalmed.uio.no.

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 RII 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.

Key Words: AKAP, cAMP, chromosome condensation, mitosis, PKA

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