Premium
Subcellular gravin localization regulates PKA compartmentalization and PKA‐dependent signaling (539.7)
Author(s) -
Schott Micah,
Maliske Ben,
Thompson Gonowolo Faith,
Grove Bryon
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.539.7
Subject(s) - microbiology and biotechnology , scaffold protein , chemistry , signal transduction , protein kinase a , cytosol , forskolin , cell signaling , receptor , kinase , biology , biochemistry , enzyme
Scaffold proteins play a critical role in cellular homeostasis by positioning signaling molecules in proximity to downstream effectors. However, some scaffold proteins do not assemble static enzyme complexes, but form dynamic signalosomes that traffic to different subcellular compartments in response to stimuli. Gravin (AKAP12) ‐ a multivalent scaffold linked to cell cycle progression, cellular migration, β2‐adrenergic receptor regulation, and hippocampal learning and memory ‐ anchors PKA and other enzymes to the plasma membrane but is redistributed to the cytosol after [Ca2+]i elevation. We postulate that gravin redistribution represents a novel mechanism for cross‐talk between Ca2+‐dependent and cAMP‐dependent signaling pathways. To assess this, we measured the impact of gravin localization on compartmentalized PKA activity using the PKA FRET biosensor AKAR3. Expression of gravin in cells lacking endogenous gravin caused an increase in forskolin‐dependent PKA activity in AKAR3 constructs targeted to the plasma membrane when compared to control cells lacking gravin or expressing a gravin construct lacking the PKA‐binding domain. Expression of a gravin mutant with reduced membrane localization showed no increase in membrane PKA activity compared to control cells lacking gravin. Interestingly, gravin expression caused a decrease in forskolin‐dependent PKA activity in cytosolic AKAR3 constructs compared to control cells lacking gravin. These results confirm that gravin localization regulates PKA signaling and support the hypothesis that gravin mediates cross‐talk between Ca2+ and cAMP‐dependent signaling in functions such as in cell cycle progression, cellular migration, β2‐adrenergic receptor regulation, and hippocampal learning and memory. Based on these results, dynamics in scaffold protein localization likely represents an important paradigm for the regulation of cellular signaling networks. Grant Funding Source : NIH P30GM103329