PKA RIα subunit is localized to MVBs by the A-kinase–anchoring protein AKAP11 when disassociated from the PKA catalytic subunit

Abramoff

Amieux

Antonius Koller

Banky

Bergold

Boeshans

Boshart

Brandon

Brennan

Bubis

Burns-Hamuro

Burton

Chaturvedi

Chen

Clague

Clegg

Eggers

Felder

Garnis

Goel

Guido M. Gaietta

Gupte

Guy A. Perkins

Hegde

Herberg

Imaizumi-Scherrer

Jahnsen

John D. Scott

Jones

Kammer

Katzmann

Kersey

Kirschner

Kuma

Laxminarayana

Lester

Levy

Mark H. Ellisman

Mason R. Mackey

Mavrakis

McKnight

Michele E. Day

Miller

Mira Sastri

Okutsu

Orellana

Reggiori

Reimann

Reinton

Rubin

Sarma

Scott

Steinberg

Susan S. Taylor

Takata

Tanner

Thiele

Tortora

Uhler

van Niel

Veugelers

Wong

Yang

Yuan

English

PubMed

Although RII protein kinase A (PKA) regulatory subunits are constitutively localized to discrete cellular compartments through binding to A-kinase–anchoring proteins (AKAPs), RI subunits are primarily diffuse in the cytoplasm. In this paper, we report a novel AKAP-dependent localization of RIα to distinct organelles, specifically, multivesicular bodies (MVBs). This localization depends on binding to AKAP11, which binds tightly to free RIα or RIα in complex with catalytic subunit (holoenzyme). However, recruitment to MVBs occurs only with the release of PKA catalytic subunit (PKAc). This recruitment is reversed by reassociation with PKAc, and it is disrupted by the presence of AKAP peptides, mutations in the RIα AKAP-binding site, or knockdown of AKAP11. Cyclic adenosine monophosphate binding not only unleashes active PKAc but also leads to the targeting of AKAP11:RIα to MVBs. Therefore, we show that the RIα holoenzyme is part of a signaling complex with AKAP11, in which AKAP11 may direct RIα functionality after disassociation from PKAc. This model defines a new paradigm for PKA signaling.</jats:p

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Isoform-specific targeting of PKA to multivesicular bodies

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Isoform-specific targeting of PKA to multivesicular bodies

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