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Expression and regulation of Homer in human skeletal muscle during neuromuscular junction adaptation to disuse and exercise

Version 2 2024-06-12, 14:48
Version 1 2015-03-17, 14:27
journal contribution
posted on 2024-06-12, 14:48 authored by M Salanova, E Bortoloso, G Schiffl, M Gutsmann, DL Belavy, D Felsenberg, S Furlan, P Volpe, D Blottner
Protein calcium sensors of the Homer family have been proposed to modulate the activity of various ion channels and nuclear factor of activated T cells (NFAT), the transcription factor modulating skeletal muscle differentiation. We monitored Homer expression and subcellular localization in human skeletal muscle biopsies following 60 d of bedrest [Second Berlin Bedrest Study (BBR2-2)]. Soleus (SOL) and vastus lateralis (VL) biopsies were taken at start (pre) and at end (end) of bedrest from healthy male volunteers of a control group without exercise (CTR; n=9), a resistive-only exercise group (RE; n=7), and a combined resistive/vibration exercise group (RVE; n=7). Confocal analysis showed Homer immunoreactivity at the postsynaptic microdomain of the neuromuscular junction (NMJ) at bedrest start. After bedrest, Homer immunoreactivity decreased (CTR), remained unchanged (RE), or increased (RVE) at the NMJ. Homer2 mRNA and protein were differently regulated in a muscle-specific way. Activated NFATc1 translocates from cytoplasm to nucleus; increased amounts of NFATc1-immunopositive slow-type myonuclei were found in RVE myofibers of both muscles. Pulldown assays identified NFATc1 and Homer as molecular partners in skeletal muscle. A direct motor nerve control of Homer2 was confirmed in rat NMJs by in vivo denervation. Homer2 is localized at the NMJ and is part of the calcineurin-NFATc1 signaling pathway. RVE has additional benefit over RE as countermeasure preventing disuse-induced neuromuscular maladaptation during bedrest.

History

Journal

FASEB journal

Volume

25

Pagination

4312-4325

Location

Bethesda, Md.

eISSN

1530-6860

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal

Copyright notice

2011, FASEB

Issue

12

Publisher

Federation of American Society of Experimental Biology