title: Expression and regulation of Homer in human skeletal muscle during neuromuscular junction adaptation to disuse and exercise.
abstract: 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.
authors: Center of Space Medicine Berlin, Neuromuscular Group, Institute of Anatomy, Charité Universitätsmedizin Berlin, Campus Charité Mitte, Philippstrasse 12, 10115, Berlin, Germany. michele.salanova@charite.de
authors: Michele
authors: M
authors: Salanova
authors: Elena
authors: E
authors: Bortoloso
authors: Gudrun
authors: G
authors: Schiffl
authors: Martina
authors: M
authors: Gutsmann
authors: Daniel L
authors: DL
authors: Belavy
authors: Dieter
authors: D
authors: Felsenberg
authors: Sandra
authors: S
authors: Furlan
authors: Pompeo
authors: P
authors: Volpe
authors: Dieter
authors: D
authors: Blottner
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D001483:Base Sequence; D001510:Bed Rest / Q000009:adverse effects; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D015444:Exercise / Q000502:physiology; D005786:Gene Expression Regulation; D000072233:Homer Scaffolding Proteins; D006801:Humans; D008297:Male; D008954:Models, Biological; D009121:Muscle Denervation; D018482:Muscle, Skeletal / Q000378:metabolism*; D020966:Muscular Disorders, Atrophic / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D050778:NFATC Transcription Factors / Q000378:metabolism; D009469:Neuromuscular Junction / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D055070:Resistance Training; D015398:Signal Transduction; D014732:Vibration / Q000627:therapeutic use
chemical_list: D002352:Carrier Proteins; D017931:DNA Primers; D000072233:Homer Scaffolding Proteins; C000606626:Homer2 protein, rat; D050778:NFATC Transcription Factors; C494003:NFATC1 protein, human; D012333:RNA, Messenger; D011994:Recombinant Proteins