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The energy regulating upstream kinase complex LKB1/MO25/STRAD is a potential novel regulator of thin filament function (1081.3)
Author(s) -
Behunin Samantha,
LopezPier Marissa,
Konhilas John
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.1081.3
Subject(s) - myofilament , ampk , regulator , microbiology and biotechnology , phosphorylation , protein kinase a , protein filament , chemistry , actin , kinase , myofibril , snap , biophysics , biology , biochemistry , computer science , gene , computer graphics (images)
AMP‐activated protein kinase (AMPK) is a cellular energetic regulator that is known to modify both metabolic and contractile function in the heart. Phosphorylation by an upstream kinase complex (LKB1/MO25/STRAD; LMS) is required for AMPK activation. Yet, the relationship between the LMS, AMPK activation, and myofilament function is unknown. Accordingly, we hypothesized that the upstream kinase complex can regulate myofilament function independently or in combination with AMPK. To do this, demembranated (skinned) rat cardiac trabeculae were incubated with either the LMS or with varying ratios of the LMS with AMPK and myofilament function was measured. Skinned rat trabeculae treated with the LMS alone were desensitized to Ca2+ and had lowered maximum tension. Adding increasing amounts of AMPK in combination with LMS reversed this effect increasing Ca2+‐sensitivity of tension and maximum tension. We furthered hypothesized that the mechanism underlying this relationship is mediated through direct interaction of the LMS with thin filament proteins. Western blot analysis showed an association of the LMS with myofibrils while immunofluorescence indicated that Mo25 co‐localizes with the phalloidin stained thin filament. In conclusion, the LMS has been identified as a potential novel regulator of myofilament function perhaps through a direct interaction with the thin filament. Grant Funding Source : T32HL07249