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

Salanova, Michele, Bortoloso, Elena, Schiffl, Gudrun, Gutsmann, Martina, Belavý, Daniel L., Felsenberg, Dieter, Furlan, Sandra, Volpe, Pompeo and Blottner, Dieter 2011, Expression and regulation of Homer in human skeletal muscle during neuromuscular junction adaptation to disuse and exercise, FASEB journal, vol. 25, no. 12, pp. 4312-4325, doi: 10.1096/fj.11-186049.

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Title Expression and regulation of Homer in human skeletal muscle during neuromuscular junction adaptation to disuse and exercise
Author(s) Salanova, Michele
Bortoloso, Elena
Schiffl, Gudrun
Gutsmann, Martina
Belavý, Daniel L.ORCID iD for Belavý, Daniel L.
Felsenberg, Dieter
Furlan, Sandra
Volpe, Pompeo
Blottner, Dieter
Journal name FASEB journal
Volume number 25
Issue number 12
Start page 4312
End page 4325
Total pages 14
Publisher Federation of American Society of Experimental Biology
Place of publication Bethesda, Md.
Publication date 2011-12
ISSN 1530-6860
Keyword(s) Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Cell Biology
Life Sciences & Biomedicine - Other Topics
postsynaptic signaling
Summary 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.
Language eng
DOI 10.1096/fj.11-186049
Field of Research 110699 Human Movement and Sports Science not elsewhere classified
Socio Economic Objective 920299 Health and Support Services not elsewhere classified
HERDC Research category C1.1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2011, FASEB
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