{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:20:36Z","timestamp":1760145636049,"version":"build-2065373602"},"reference-count":45,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T00:00:00Z","timestamp":1722902400000},"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","50WB0521-0821-1121-1421"],"award-info":[{"award-number":["50WB2116","50WB0521-0821-1121-1421"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We investigated the shuttling of Homer protein isoforms identified in soluble (cytosolic) vs. insoluble (membrane\u2013cytoskeletal) fraction and Homer protein\u2013protein interaction\/activation in the deep postural calf soleus (SOL) and non-postural gastrocnemius (GAS) muscles of het\u2212\/\u2212 mice, i.e., mice with an autosomal recessive variant responsible for a vestibular disorder, in order to further elucidate a) the underlying mechanisms of disrupted vestibular system-derived modulation on skeletal muscle, and b) molecular signaling at respective neuromuscular synapses. Heterozygote mice muscles served as the control (CTR). An increase in Homer cross-linking capacity was present in the SOL muscle of het\u2212\/\u2212 mice as a compensatory mechanism for the altered vestibule system function. Indeed, in both fractions, different Homer immunoreactive bands were detectable, as were Homer monomers (~43\u201348 kDa), Homer dimers (~100 kDa), and several other Homer multimer bands (&gt;150 kDA). The het\u2212\/\u2212\u00a0GAS particulate fraction showed no Homer dimers vs. SOL. The het\u2212\/\u2212\u00a0SOL soluble fraction showed a twofold increase (+117%, p \u2264 0.0004) in Homer dimers and multimers. Homer monomers were completely absent from the SOL independent of the animals studied, suggesting muscle-specific changes in Homer monomer vs. dimer expression in the postural SOL vs. the non-postural GAS muscles. A morphological assessment showed an increase (+14%, p \u2264 0.0001) in slow\/type-I myofiber cross-sectional area in the SOL of het\u2212\/\u2212 vs. CTR mice. Homer subcellular immuno-localization at the neuromuscular junction (NMJ) showed an altered expression in the SOL of het\u2212\/\u2212mice, whereas only not-significant changes were found for all Homer isoforms, as judged by RT-qPCR analysis. Thus, muscle-specific changes, myofiber properties, and neuromuscular signaling mechanisms share causal relationships, as highlighted by the variable subcellular Homer isoform expression at the instable NMJs of vestibular lesioned het\u2212\/\u2212 mice.<\/jats:p>","DOI":"10.3390\/ijms25168577","type":"journal-article","created":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T11:54:19Z","timestamp":1722945259000},"page":"8577","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Increased Homer Activity and NMJ Localization in the Vestibular Lesion het\u2212\/\u2212 Mouse soleus Muscle"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8917-2962","authenticated-orcid":false,"given":"Gabor","family":"Trautmann","sequence":"first","affiliation":[{"name":"Institute of Integrative Neuroanatomy, Neuromuscular Signaling and System, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Philippstrasse 12, 10115 Berlin, Germany"},{"name":"Center of Space Medicine Berlin, 10115 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2752-5232","authenticated-orcid":false,"given":"Katharina","family":"Block","sequence":"additional","affiliation":[{"name":"Institute of Integrative Neuroanatomy, Neuromuscular Signaling and System, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Philippstrasse 12, 10115 Berlin, Germany"},{"name":"Center of Space Medicine Berlin, 10115 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Gutsmann","sequence":"additional","affiliation":[{"name":"Institute of Integrative Neuroanatomy, Neuromuscular Signaling and System, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Philippstrasse 12, 10115 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"St\u00e9phane","family":"Besnard","sequence":"additional","affiliation":[{"name":"UR VERTEX 7480, CHU de Caen, Universit\u00e9 de Caen Normandie, 10115 Caen, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Furlan","sequence":"additional","affiliation":[{"name":"C.N.R. Institute of Neuroscience, 14000 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9049-7692","authenticated-orcid":false,"given":"Pierre","family":"Denise","sequence":"additional","affiliation":[{"name":"COMETE U1075, INSERM, CYCERON, CHU de Caen, Normandie Universit\u00e9, Universit\u00e9 de Caen Normandie, 10115 Caen, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0151-1585","authenticated-orcid":false,"given":"Pompeo","family":"Volpe","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Padova, 14000 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0355-3340","authenticated-orcid":false,"given":"Dieter","family":"Blottner","sequence":"additional","affiliation":[{"name":"Institute of Integrative Neuroanatomy, Neuromuscular Signaling and System, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Philippstrasse 12, 10115 Berlin, Germany"},{"name":"Center of Space Medicine Berlin, 10115 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7066-3876","authenticated-orcid":false,"given":"Michele","family":"Salanova","sequence":"additional","affiliation":[{"name":"Institute of Integrative Neuroanatomy, Neuromuscular Signaling and System, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Philippstrasse 12, 10115 Berlin, Germany"},{"name":"Center of Space Medicine Berlin, 10115 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1146\/annurev.neuro.31.060407.125555","article-title":"Vestibular system: The many facets of a multimodal sense","volume":"31","author":"Angelaki","year":"2008","journal-title":"Annu. 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