{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:12:43Z","timestamp":1792109563717,"version":"4.4.0"},"reference-count":50,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T00:00:00Z","timestamp":1669766400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Federal Ministry for Economic Affairs and Climate Action (BMWK)","award":["50WB2116"],"award-info":[{"award-number":["50WB2116"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Accelerated postsynaptic remodelling and disturbance of neuromuscular transmission are common features of autoimmune neurodegenerative diseases. Homer protein isoform expression, crosslinking activity and neuromuscular subcellular localisation are studied in mouse hind limb muscles of an experimentally induced autoimmune model of Myasthenia Gravis (EAMG) and correlated to motor end plate integrity. Soleus (SOL), extensor digitorum longus (EDL) and gastrocnemius (GAS) skeletal muscles are investigated. nAChR membrane clusters were studied to monitor neuromuscular junction (NMJ) integrity. Fibre-type cross-sectional area (CSA) analysis is carried out in order to determine the extent of muscle atrophy. Our findings clearly showed that crosslinking activity of Homer long forms (Homer 1b\/c and Homer2a\/b) are decreased in slow-twitch and increased in fast-twitch muscle of EAMG whereas the short form of Homer that disrupts Homer crosslinking (Homer1a) is upregulated in slow-twitch muscle only. Densitometry analysis showed a 125% increase in Homer protein expression in EDL, and a 45% decrease in SOL of EAMG mice. In contrast, nAChR fluorescence pixel intensity decreased in endplates of EAMG mice, more distinct in type-I dominant SOL muscle. Morphometric CSA of EAMG vs. control (CTR) revealed a significant reduction in EDL but not in GAS and SOL. Taken together, these results indicate that postsynaptic Homer signalling is impaired in slow-twitch SOL muscle from EAMG mice and provide compelling evidence suggesting a functional coupling between Homer and nAChR, underscoring the key role of Homer in skeletal muscle neurophysiology.<\/jats:p>","DOI":"10.3390\/ijms232315052","type":"journal-article","created":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T01:54:31Z","timestamp":1669859671000},"page":"15052","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Opposite Regulation of Homer Signal at the NMJ Postsynaptic Micro Domain between Slow- and Fast-Twitch Muscles in an Experimentally Induced Autoimmune Myasthenia Gravis (EAMG) Mouse Model"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2063-1849","authenticated-orcid":false,"given":"Martin","family":"Schubert","sequence":"first","affiliation":[{"name":"Institute of Integrative Neuroanatomy, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin and Berlin Institute of Health, 10115 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7111-6970","authenticated-orcid":false,"given":"Andreas","family":"Pelz","sequence":"additional","affiliation":[{"name":"Department of Experimental Neurology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, 10115 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabor","family":"Trautmann","sequence":"additional","affiliation":[{"name":"Institute of Integrative Neuroanatomy, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin and Berlin Institute of Health, 10115 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2752-5232","authenticated-orcid":false,"given":"Katharina","family":"Block","sequence":"additional","affiliation":[{"name":"Center of Space Medicine Berlin, Neuromuscular Signaling and System, 10115 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6366-3552","authenticated-orcid":false,"given":"Sandra","family":"Furlan","sequence":"additional","affiliation":[{"name":"C.N.R. Institute of Neuroscience, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Gutsmann","sequence":"additional","affiliation":[{"name":"Institute of Integrative Neuroanatomy, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin and Berlin Institute of Health, 10115 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siegfried","family":"Kohler","sequence":"additional","affiliation":[{"name":"Department of Experimental Neurology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, 10115 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pompeo","family":"Volpe","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Padova, 35122 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0355-3340","authenticated-orcid":false,"given":"Dieter","family":"Blottner","sequence":"additional","affiliation":[{"name":"Institute of Integrative Neuroanatomy, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin and Berlin Institute of Health, 10115 Berlin, Germany"},{"name":"Center of Space Medicine Berlin, Neuromuscular Signaling and System, 10115 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7233-5342","authenticated-orcid":false,"given":"Andreas","family":"Meisel","sequence":"additional","affiliation":[{"name":"Department of Experimental Neurology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, 10115 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7066-3876","authenticated-orcid":false,"given":"Michele","family":"Salanova","sequence":"additional","affiliation":[{"name":"Institute of Integrative Neuroanatomy, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin and Berlin Institute of Health, 10115 Berlin, Germany"},{"name":"Center of Space Medicine Berlin, Neuromuscular Signaling and System, 10115 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1038\/386284a0","article-title":"Homer: A protein that selectively binds metabotropic glutamate receptors","volume":"386","author":"Brakeman","year":"1997","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4312","DOI":"10.1096\/fj.11-186049","article-title":"Expression and regulation of Homer in human skeletal muscle during neuromuscular junction adaptation to disuse and exercise","volume":"25","author":"Salanova","year":"2011","journal-title":"FASEB J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"re8","DOI":"10.1126\/stke.2002.137.re8","article-title":"Homer as both a scaffold and transduction molecule","volume":"2002","author":"Fagni","year":"2002","journal-title":"Sci. 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