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The Effect of Membrane Composition on PLCβ and Gα q ‐mediated Activation
Author(s) -
Hudson Brian.,
Hyun SeokHee,
Thompson David H.,
Lyon Angeline M.
Publication year - 2018
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.2018.32.1_supplement.815.1
Subject(s) - diacylglycerol kinase , heterotrimeric g protein , g protein coupled receptor , gq alpha subunit , second messenger system , phospholipase c , microbiology and biotechnology , phosphoinositide phospholipase c , effector , g protein , chemistry , membrane , intracellular , biology , biochemistry , signal transduction , protein kinase c
Phospholipase C β (PLCβ) enzymes are peripheral membrane proteins that are required for normal cardiovascular function and whose dysregulation results in cardiovascular disease. PLCβ hydrolyzes phosphatidylinositiol‐4,5‐bisphosphate (PIP 2 ) to produce the potent second messengers inositol‐1,4,5‐triphosphate (IP 3 ) and diacylglycerol (DAG), which increase intracellular Ca 2+ and activate protein kinase C. PLCβ has low basal activity, but is activated downstream of G protein‐coupled receptors (GPCRs) through direct interactions with the heterotrimeric G protein subunits Gα q and Gβγ. While G proteins stimulate activity, they are insufficient for full activation. This suggests that the membrane is required for full activation. However, the molecular basis for how the membrane and its properties contribute to PLCβ adsorption, activity, and Gα q ‐dependent activation are not well understood. We seek to understand how the membrane composition and its surface charge regulate adsorption of PLCβ to the membrane and promote interfacial activation, and the role of Gα q in this process. Using a model membrane system, we are applying an innovative combination of atomic force microscopy, Raman spectroscopy and biochemical assays to begin understanding how the membrane itself and Gα q regulate PLCβ activation. These studies provide the first structure‐based approach to understanding how the cell membrane regulates the activity of this essential effector enzyme. Support or Funding Information American Heart Association Scientist Development Grant (16SDG29920017) to A.M.L.; Purdue Doctoral Fellowship to B.N.H.; Purdue Center for Cancer Research This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .