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Phospholipase C beta 1b is the PLC splice variant that selectively mediates α1‐receptor and Gq‐coupled hypertrophy in cardiomyocytes
Author(s) -
Filtz Theresa Marie,
Grubb David Robert,
Woodcock Elizabeth Ann
Publication year - 2009
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.23.1_supplement.582.1
Subject(s) - phospholipase c , gq alpha subunit , g protein , heterotrimeric g protein , microbiology and biotechnology , biology , muscle hypertrophy , splice , medicine , endocrinology , phenylephrine , signal transduction , gene , biochemistry , blood pressure
Activation of the heterotrimeric G protein Gq in cardiomyocytes leads to pathological hypertrophy and apoptosis in vivo and in vitro . As the immediate downstream effector of Gq, phospholipase Cβ (PLCβ) may mediate these responses. Neonatal rat cardiomyocytes (NRVM) express the two splice variants of PLCβ1, PLCβ1a (150 kDa) and PLCβ1b (140 kDa), which differ only in their extreme C‐termini. PLCβ1a is localized in the cytoplasm of NRVM whereas PLCβ1b targets to the sarcolemma through its unique C terminal domain. Adenoviral over‐expression of PLCβ1b in NRVM caused substantial hypertrophy followed by apoptosis; whereas over‐expression of PLCβ1a did not. Adenovirus expression in NRVM of an inhibitory mini‐gene incorporating the entire unique C‐terminal sequences of PLCβ1b inhibited PLC activity and completely suppressed hypertrophy induced with phenylephrine/propanolol or Gq over‐expression. This study indicates a major role for PLCβ1b in Gq‐mediated pathology and suggests that PLCβ1b but not PLCβ1a is responsible for Gq responses in NRVM. The PLCβ1b/sarcolemmal interface provides a potentially selective target for blocking Gq‐mediated pathology. This work was sponsored by the NH&MRC (Australia).