Increased Homer Activity and NMJ Localization in the Vestibular Lesion Mouse Muscle.

We investigated the shuttling of Homer protein isoforms identified in soluble (cytosolic) vs. insoluble (membrane-cytoskeletal) fraction and Homer protein-protein interaction/activation in the deep postural calf ( and non-postural () muscles of 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 muscle of 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 (~43-48 kDa), Homer dimers (~100 kDa), and several other Homer multimer bands (>150 kDA). The particulate fraction showed no Homer dimers vs. . The soluble fraction showed a twofold increase (+117%, ≤ 0.0004) in Homer dimers and multimers. Homer monomers were completely absent from the independent of the animals studied, suggesting muscle-specific changes in Homer monomer vs. dimer expression in the postural vs. the non-postural muscles. A morphological assessment showed an increase (+14%, ≤ 0.0001) in slow/type-I myofiber cross-sectional area in the of vs. CTR mice. Homer subcellular immuno-localization at the neuromuscular junction (NMJ) showed an altered expression in the of mice, 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 mice.