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Kvβ subunit interacts with NEDD4 leading to decreased mouse skeletal muscle size.
Author(s) -
Tipparaju Srinivas,
Tur Jared,
Brotto Marco,
Chapalamadagu Kalyan
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.768.3
Subject(s) - skeletal muscle , protein subunit , phenotype , myocyte , biology , myogenesis , gene knockdown , wild type , skeletal muscle fibers , microbiology and biotechnology , medicine , chemistry , endocrinology , genetics , cell culture , gene , mutant
Background The voltage‐gated potassium channel subunits 1–3 play significant physiological roles in excitable and non‐excitable tissues. However, the precise nature of its expression and functional identify in skeletal muscle remains unknown. Hypothesis Therefore we hypothesized that Kvβ subunits play a significant physiological role in the skeletal muscle. Methods and Results In the present study we identified that the voltage gated potassium channel subunit Kvβ interacts with NEDD4 in skeletal muscle. Previous research indicated a possible interaction with Kvβ and NEDD4 through pathway analysis. Utilizing immunoprecipitate pulldown technique, wild type skeletal muscle homogenates were incubated with Kvβ2 coated magnetic beads and run on SDS‐PAGE and immunoblotted with NEDD4 antibody demonstrating a visible band. Using a genetic deletion of kcnab we identified that the size of the major hind limb muscle is significantly decreased in Kvβ KO mice compared with wild type mice. Therefore we explored the underlying causes for this phenotype since Kvβ is ubiquitously expressed in skeletal muscle. Based on our investigation Kvβ plays a major role in muscle differentiation and overall size, however the proliferation aspect in skeletal muscle at least in the in vitro level remains unaffected. We utilized targeted siRNA knockdown approached to confirm these findings. In addition, tissue analysis reveals that the MHCI fiber type is significantly increased in Kvβ KO group compared with wild type. Conclusion Overall, this is the first study demonstrating that Kvβ2 plays a significant role in determining the size of the skeletal muscle and phenotype. Support or Funding Information This Research work was funded by National Institutes of Health (NIH) Grant R01‐HL‐102171 (S. M. Tipparaju). This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .