Disease relevance of myosin

• Characterization of a myosin-like antigen from Onchocerca volvulus [1].

High impact information on myosin

• Other alleles alter the site at which myosin binds actin [2].
• The most strongly dominant alleles alter highly conserved residues of the myosin ATP binding site, indicating that functions of the myosin ATPase are important for thick filament assembly [2].
• The body wall muscle cells of the nematode, Caenorhabditis elegans, contain two unique types of myosin heavy chain, A and B. We have utilized an immunochemical approach to define the structural location of these two myosins within body wall muscle thick filaments [3].
• The myosin B antibody reacts with the polar regions of all filaments but does not react with a central 0.9 micron zone [3].
• Mutant embryos in which cleavage arrests prematurely also generate cells that produce myosin and paramyosin [4].

Biological context of myosin

• This phenotype was suppressed by inhibiting muscle contraction by a myosin mutation, but it was enhanced by tetramisole-induced hypercontraction [5].
• Functions of the myosin ATP and actin binding sites are required for C. elegans thick filament assembly [2].
• Three different X-chromosome clones, including part of an actin gene, part of a myosin heavy chain gene, and all of two myosin light chain genes, feminize chromosomal males [6].
• We show that a regulatory myosin light chain normally becomes phosphorylated on the apical side of ingressing cells at a conserved site that can lead to myosin-filament formation and contraction of actomyosin networks and that this phosphorylation depends on Wnt signaling [7].
• Overall, nematode sperm motility illustrates that cell locomotion can be generated by cytoskeletal dynamics alone without the use of myosin-like motor proteins [8].

Anatomical context of myosin

• These results indicate that the linear structures represent nascent assemblies containing myosin and pm in which the proteins interact differently than in wild-type thick filaments of myofibrils [9].
• By staining mutant embryos for myosin and actin we have recognized five distinct classes of genes: mutations in four genes disrupt the assembly of thick and thin filaments into the myofilament lattice as well as the polarized location of these components to the sarcolemma [10].
• Myosin heavy chains C and D are limited to the pharyngeal muscle cells, whereas myosin heavy chains A and B are localized not only within the sarcomeres of body wall muscle cells, as reported previously, but to the smooth muscle cells of the minor groups as well [11].
• Loss of RHO-1 activity causes defects in the early organization of the myosin cytoskeleton but does not inhibit segregation of myosin to the anterior [12].
• CONCLUSIONS: C. elegans myosin VI has an important role in the unequal partitioning of both organelles and cytoskeletal components, a novel role for this class of motor protein [13].

Associations of myosin with chemical compounds

• Multiple lines of evidence support a model in which UNC-98 links integrin-associated proteins to myosin in thick filaments at M-lines [14].
• The SH3 domains of src and other nonreceptor tyrosine kinases have been shown to associate with the motif PXXP, where P and X stand for proline and an unspecified amino acid, but a motif that binds to the SH3 domain of myosin has thus far not been characterized [15].
• However, particular regions were detected: - a polyglutamine repeat domain in the N-terminal part of the protein, - four peptide sequences associated with GTP-binding sites, - a sequence with slight homology to the rod tail of Caenorhabditis elegans myosin II, -a sequence with homology to a human kinesin motor domain [16].
• The other three are in the light meromyosin portion, assigned at residues 572, 600 and 770 on the basis of homology between the amino acid sequence in the vicinity of these thiols and that of the rod of nematode myosin (McLachlan, A.D. and Karn, J. (1982) Nature 299, 226-231) [17].

Physical interactions of myosin

• The myosin binds to F actin in a polar and ATP-sensitive manner, and the Mg2+-ATPase is activated by either F actin or nematode thin filaments [18].
• The major paramyosin species interacts with the two genetically specified myosin heavy chain isoforms [19].

Regulatory relationships of myosin

• Both myosin control and actin control operate simultaneously in the majority of invertebrates tested [20].

Other interactions of myosin

• Sperm of the nematode, Ascaris suum, are amoeboid cells that do not require actin or myosin to crawl over solid substrata [21].
• However, the myosin mutation showed much weaker suppression of the phenotypes of ADF/cofilin or AIP1 mutants than tropomyosin depletion [22].
• Actin comprises less than 0.02% of the proteins in sperm, and myosin is undetectable [23].
• The N-terminal region of paramyosin has significant similarity to the non-helical C-terminal region of the two body wall myosin heavy chains of C. elegans [24].
• The hum-1, hum-2 and hum-3 genes have been mapped by extrapolation near previously uncharacterized mutations, several of which are lethal, identifying potentially essential unconventional myosin genes in C. elegans [25].

Analytical, diagnostic and therapeutic context of myosin

• By immunofluorescence microscopy, myosin B antibodies label the thick filament-containing A-bands of body wall muscle with the exception of a thin gap at the center of each A-band, and myosin A antibodies react to form a medial fluorescent stripe within each A-band [3].

References