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Mechanisms and Regulation of PLCβ and its Effects on Membrane Adsorption
Author(s) -
Hudson Brian,
Hyun SeokHee,
Thompson David H,
Lyon Angeline M
Publication year - 2017
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.31.1_supplement.816.8
Subject(s) - diacylglycerol kinase , phospholipase c , microbiology and biotechnology , membrane , second messenger system , phosphatidylinositol , effector , gq alpha subunit , inositol , chemistry , biochemistry , signal transduction , biophysics , biology , g protein , receptor , protein kinase c
Phospholipase C (PLC) enzymes are peripheral membrane proteins that are activated by the G q subfamily of G‐protein coupled receptors. The enzymes hydrolyze the membrane component phosphatidylinositol‐4, 5‐bisphosphate (PIP 2 ) into two potent second messengers, inositol‐1,4,5‐triphosphate (IP 3 ) and diacylglycerol (DAG), in response to diverse stimuli. PLCβ enzymes are required for normal cardiovascular function and increased expression is associated with arrhythmias, hypertrophy, and heart failure. Previous studies have shown the C‐terminal domains of PLCβ contribute to its regulation and membrane association. However, there is no structural information on how the membrane and C‐terminal domains contribute to PLCβ regulation. We seek to understand how the membrane enhances association and promotes conformational changes within PLCβ that increase catalytic activity. Beginning with model membrane systems, we are applying atomic force microscopy and complementary biochemical assays to evaluate the role of the C‐terminal regulatory domains in membrane adsorption and activity. We are also investigating how the physical and chemical properties of the membrane itself, e.g. surface charge, fluidity, and composition, regulate PLCβ adsorption and activation. These studies provide the first structure‐based approach to understanding how the cell membrane itself regulates the activity of this essential effector enzyme. Support or Funding Information The Purdue Doctoral Fellowship