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Arch Biochem Biophys. 2016 Jul 1;601:32-41. doi: 10.1016/j.abb.2016.03.012. Epub 2016 Mar 10.

Liver Kinase B1 complex acts as a novel modifier of myofilament function and localizes to the Z-disk in cardiac myocytes.

Author information

1
Department of Physiology, University of Arizona, Tucson, AZ, USA; Sarver Molecular Cardiovascular Research Program, University of Arizona, Tucson, AZ, USA.
2
Sarver Molecular Cardiovascular Research Program, University of Arizona, Tucson, AZ, USA; Department of Biomedical Engineering, University of Arizona, Tucson, AZ, USA.
3
Sarver Molecular Cardiovascular Research Program, University of Arizona, Tucson, AZ, USA; Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ, USA.
4
Sarver Molecular Cardiovascular Research Program, University of Arizona, Tucson, AZ, USA; Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ, USA.
5
Department of Physiology, University of Arizona, Tucson, AZ, USA; Sarver Molecular Cardiovascular Research Program, University of Arizona, Tucson, AZ, USA. Electronic address: konhilas@arizona.edu.

Abstract

Contractile perturbations downstream of Ca(2+) binding to troponin C, the so-called sarcomere-controlled mechanisms, represent the earliest indicators of energy remodeling in the diseased heart [1]. Central to cellular energy "sensing" is the adenosine monophosphate-activated kinase (AMPK) pathway, which is known to directly target myofilament proteins and alter contractility [2-6]. We previously showed that the upstream AMPK kinase, LKB1/MO25/STRAD, impacts myofilament function independently of AMPK [5]. Therefore, we hypothesized that the LKB1 complex associated with myofilament proteins and that alterations in energy signaling modulated targeting or localization of the LKB1 complex to the myofilament. Using an integrated strategy of myofilament mechanics, immunoblot analysis, co-immunoprecipitation, mass spectroscopy, and immunofluorescence, we showed that 1) LKB1 and MO25 associated with myofibrillar proteins, 2) cellular energy stress re-distributed AMPK/LKB1 complex proteins within the sarcomere, and 3) the LKB1 complex localized to the Z-Disk and interacted with cytoskeletal and energy-regulating proteins, including vinculin and ATP Synthase (Complex V). These data represent a novel role for LKB1 complex proteins in myofilament function and myocellular "energy" sensing in the heart.

KEYWORDS:

Contractility; Liver Kinase B1 (LKB1); Myofibril; Myofilament; Vinculin; Z-disk

PMID:
26971467
PMCID:
PMC4899161
DOI:
10.1016/j.abb.2016.03.012
[Indexed for MEDLINE]
Free PMC Article

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