Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The shaker-2 mouse with inherited inner ear disease suffers from deafness and a shaking-waltzing behavior. The hair cell type I in cristae ampullares and maculae utriculi show a specific pathology, featuring fusion of the stereocilia and presence of a rod-shaped inclusion body. The inclusion body is composed of filaments that could be identified as the protein actin by the method of decoration with subfragment S-1 of myosin. The functional polarity was determined, and S-1 fragments were found to point apically, that is, from the nucleus up toward the cuticular plate. These observations are identical to those earlier described in the waltzing guinea pig. It is concluded that the identical pathology at a cellular level in two different species may indicate a pathologic disorder in a process fundamental to the normal development of this type of hair cell.
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PMID:Rods of actin filaments in type I hair cells of the Shaker-2 mouse. 688 51

Manipulation of the single conventional myosin heavy chain (mhc) gene in Dictyostelium discoideum (Dd) has delineated an essential role for the filament-forming, or light meromyosin (LMM) domain of the myosin molecule in cytokinesis, development, and in the capping of cell surface receptors (see Spudich: Cell Regulation 1:1-11, 1989; Egelhoff et al.: Journal of Cell Biology, 112:677-688, 1991a). In order to assess the functional relationship between sarcomeric and cytoplasmic myosins, a chimeric gene encoding the Dd myosin head and subfragment 2 fused to rat beta cardiac LMM was transfected into both wild-type and Dd mhc null cells. Chimeric myosin was organized into dense cortical patches in the cytoplasm of both wild-type and Dd mhc null cells. Although null cells expressing chimeric mhc at approximately 10% of Dd mhc levels were unable to grow in shaking suspension or to complete development, chimeric myosin was able to rescue capping of cell surface receptors, to associate with filamentous actin, and to localize to the correct subcellular position during aggregation. Deletion of 29 amino acids in the rod corresponding to a previously defined filament assembly competent region eliminated the cortical patches and the posterior localization during chemotaxis. Taken together, these observations suggest that sarcomeric and cytoplasmic myosin rods are functionally interchangeable in several aspects of nonmuscle motility.
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PMID:Functional analysis of a cardiac myosin rod in Dictyostelium discoideum. 806 39

Cytokinesis is a final step in cell division. Dictyostelium cells, a model organism for the study of cytokinesis, have multiple modes, denoted cytokinesis A, B, C, and D. All these modes have been mainly investigated using cells adhering to the substratum although they can grow in shaking suspension culture. Here, we observed how cells divide without adhering to the substratum using a new non-adhesive material. These detached cells formed the cleavage furrow but eventually failed in the final abscission. Thus, the cells cannot divide without adhesion, suggesting that they cannot divide only through the conventional cytokinesis A. However, in a long-term culture, the detached cells adhered each other to form multicellular aggregates and divided properly in these aggregates. Myosin II-null cells also formed such aggregates but could not divide in the aggregates. Several lines of experiments using mutant cells showed that the process of cytokinesis in multicellular aggregates is a novel mode utilizing a confined space in the aggregate in a myosin II-dependent manner. These results shed light on a poorly characterized mechanism of cytokinesis in multicellular spheroids or tissues. We propose to redefine and classify multiple modes of cytokinesis.
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PMID:A novel mode of cytokinesis without cell-substratum adhesion. 2925 56

Encoding the slow skeletal muscle isoform of myosin binding protein-C, MYBPC1 is associated with autosomal dominant and recessive forms of arthrogryposis. The authors describe a novel association for MYBPC1 in four patients from three independent families with skeletal muscle weakness, myogenic tremors, and hypotonia with gradual clinical improvement. The patients carried one of two de novo heterozygous variants in MYBPC1, with the p.Leu263Arg variant seen in three individuals and the p.Leu259Pro variant in one individual. Both variants are absent from controls, well conserved across vertebrate species, predicted to be damaging, and located in the M-motif. Protein modeling studies suggested that the p.Leu263Arg variant affects the stability of the M-motif, whereas the p.Leu259Pro variant alters its structure. In vitro biochemical and kinetic studies demonstrated that the p.Leu263Arg variant results in decreased binding of the M-motif to myosin, which likely impairs the formation of actomyosin cross-bridges during muscle contraction. Collectively, our data substantiate that damaging variants in MYBPC1 are associated with a new form of an early-onset myopathy with tremor, which is a defining and consistent characteristic in all affected individuals, with no contractures. Recognition of this expanded myopathic phenotype can enable identification of individuals with MYBPC1 variants without arthrogryposis.
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PMID:Heterozygous variants in MYBPC1 are associated with an expanded neuromuscular phenotype beyond arthrogryposis. 3126 22