Disease relevance of MYH1

• We propose the term myosin storage myopathy for this disease [1].
• Laing early onset distal myopathy: slow myosin defect with variable abnormalities on muscle biopsy [2].
• Here we show that mutations in the embryonic myosin heavy chain (MYH3) gene cause Freeman-Sheldon syndrome (FSS), one of the most severe multiple congenital contracture (that is, arthrogryposis) syndromes, and nearly one-third of all cases of Sheldon-Hall syndrome (SHS), the most common distal arthrogryposis [3].
• 24 h after adenoviral exposure, MyoD-converted cultures were injected into regenerating muscle of immunodeficient (severe combined immunodeficiency/beige) mice, where they gave rise to beta-galactosidase positive, centrally nucleated fibers expressing human myosin heavy chains [4].
• Several mutations within the gene coding for the cardiac beta myosin heavy chain (designed MYH7) have been shown to be responsible for Familial Hypertrophic Cardiomyopathy (FHC) in several families, and evidence of genetic heterogeneity has been reported [5].

Psychiatry related information on MYH1

• The segment of smooth muscle regulatory light chain essential for the phosphorylation dependent activation of actomyosin motor activity and the binding of myosin heavy chain was identified [6].
• Cardiac myosin binding protein C gene is specifically expressed in heart during murine and human development [7].
• After exercise, the recovery of phosphocreatine-an index of oxidative metabolic capacity of the muscle-was slower in the beta myosin heavy chain group (mean half time 0.65 (0.08) minutes) than in the troponin T group (0.60 (0.17) minutes) or controls (0.48 (0.14) minutes) [8].
• In hyperthyroidism, the cross-bridge movement significantly preceded tension development, suggesting that hyperthyroid myosin (V1) has a longer latency period between the shift to the vicinity of the thin filament and force development [9].
• Cooperative behavior of smooth muscle myosin [10].

High impact information on MYH1

• Kinetics shows that the binding of myosin to actin is a two-step process which affects ATP and ADP affinity [11].
• Molecular genetics of myosin [12].
• Structural and biochemical studies suggest that the position of tropomyosin (Tm) and troponin (Tn) on the thin filament determines the interaction of myosin with the binding sites on actin [13].
• 3) The initial rate of force development depends mostly on the extent of Ca(2+) activation of the thin filament and myosin kinetic properties but depends little on the initial force level [13].
• Second, the technology to measure picoNewton forces and nanometer distances has provided direct determinations of the force and step length generated by a single myosin molecule interacting with a single actin filament [14].

Chemical compound and disease context of MYH1

• Compounds interfering with actin function, including phalloidin, the catalytic subunit of Clostridium botulinum C2 toxin, and N-ethylmaleimide-treated myosin S1 fragments were microinjected into the axon [15].
• Stimulation of cardiac myosin adenosine triphosphatase in thyrotoxicosis [16].
• The presence of ventricular myosin light chains in the atria of children with congenital heart disease was demonstrated by two-dimensional polyacrylamide gel electrophoresis, peptide mapping, and Western blot analysis [17].
• All Lewis rats immunized with the rod exhibited severe myocarditis, and the immunization of the cyanogen bromide-cleaved peptide equivalent to human beta-cardiac myosin heavy chain RDCB9 (residues 1070 to 1165) induced moderate myocarditis [18].
• Treatment of ovarian cancer cells with alendronate resulted in inactivation of Rho, changes of cell morphology, loss of stress fiber formation, and focal adhesion assembly, and the suppression of phosphorylation of myosin light chain and tyrosine phosphorylation of focal adhesion proteins, which are essential processes for cell migration [19].

Biological context of MYH1

• Myosin storage myopathy associated with a heterozygous missense mutation in MYH7 [1].
• Myosin gene expression in the respiratory muscles [20].
• Two partial cDNAs (pAZMY4 and pAZMY7), coding for the porcine myosin heavy chain-2B and -beta respectively, have been isolated from a pig skeletal muscle cDNA library [21].
• Four RFLPs were detected with the putative porcine skeletal myosin heavy chain-2B probe (pAZMY4) and one RFLP was identified with the putative myosin heavy chain-beta probe (pAZMY7) [21].
• Organization of human and mouse skeletal myosin heavy chain gene clusters is highly conserved [22].

Anatomical context of MYH1

• Three major MyHC isoforms are expressed in human skeletal muscle (type I, MYH7, expressed in type 1 fibres; IIa, MYH2, expressed in 2A fibres; IIx, MYH1, expressed in 2B fibres) [23].
• The conventional myosin motor proteins that drive mammalian skeletal and cardiac muscle contraction include eight sarcomeric myosin heavy chain (MyHC) isoforms [24].
• Myosin storage myopathy is a congenital myopathy characterized by subsarcolemmal hyaline bodies in type 1 muscle fibers, which are ATPase positive and thus contain myosin [25].
• Intermuscular and intramuscular differences in myosin heavy chain composition of the human masticatory muscles [26].
• Cytoplasmic staining included stress fibers that colocalized with actin, probably as a consequence of the myosin heavy chain component of the fusion protein [27].

Associations of MYH1 with chemical compounds

• The myosin molecule is composed of two heavy (MyHC) and two light chains (MyLC) that, together with the adenosine triphosphatase (ATPase) activity, determine the functional characteristics of the fibre [20].
• The authors have identified the arginine 1845 tryptophan mutation found in the Swedish families in two isolated Belgian cases, indicating a critical role for myosin residue arginine 1845 [25].
• Expression of constitutively active forms of Akt dramatically enhances myotube formation and expression of the muscle-specific proteins MyoD, creatine kinase, myosin heavy chain, and desmin [28].
• Twenty-four are clustered around four specific locations in the myosin head that are (i) associated with the actin binding interface, (ii) around the nucleotide binding site, (iii) adjacent to the region that connects the two reactive cysteine residues, and (iv) in close proximity to the interface of the heavy chain with the essential light chain [29].
• In accordance with this negative role, reactivation of JNKs by anisomycin, in UO126-pre-treated cells, also prevents myosin expression [30].
• Our previous studies showed that UNC-98, a C2H2 Zn finger protein, acts as a linkage between UNC-97, an integrin-associated protein, and MHC A in myosin thick filaments [31].

Physical interactions of MYH1

• Characterization of the metastasis-associated protein, S100A4. Roles of calcium binding and dimerization in cellular localization and interaction with myosin [32].
• This isoform of myosin I beta appears to be in a complex with RNA polymerase II and may affect transcription [33].

Co-localisations of MYH1

• Confocal and electron microscopy revealed that nuclear myosin I beta colocalized with RNA polymerase II in an alpha-amanitin- and actinomycin D-sensitive manner [33].

Regulatory relationships of MYH1

• Addition of recombinant activin inhibited muscle development in a dose-dependent manner as measured by the number of nuclei in myosin heavy chain positive cells and creatine phosphokinase activity [34].
• Both non-glycosylated and glycosylated LIF blocked differentiation of myoblasts as measured by expression of myosin heavy chain and myotube formation [35].
• S100A4 is known to be involved in cancer cell motility by virtue of its ability to activate nonmuscle myosin [36].

Other interactions of MYH1

• Endurance training in a group of affected patients caused a shift in the expression of myosin from fast (IIx) to slow (I) isoforms but no reduction in the expression of MyHC IIa [23].
• It is allelic with myosin storage myopathy, with the commonest form of familial hypertrophic cardiomyopathy, and with one form of dilated cardiomyopathy [2].
• Anisomycin persistently activates p38 and JNKs but prevents myosin expression induced by TPA [30].
• Immunohistochemistry was supportive of skeletal muscle differentiation with at least one positive skeletal muscle-specific marker (myoglobin, MyoD1, fast skeletal muscle myosin, or myf4) [37].
• The YAC contig spans more than 2 Mb and encompasses the loci D14S283 and D14S990 and the cardiac alpha and beta myosin heavy chain genes (MYH6 and MYH7) [38].

Analytical, diagnostic and therapeutic context of MYH1

• Comparative sequence analysis of the complete human sarcomeric myosin heavy chain family: implications for functional diversity [24].
• Significantly decreased staining with two markers of myogenic differentiation, myosin in keloidal fibroblasts (P = 0.002) and desmin (P = 0.007) in normal fibroblasts, could also be detected after treatment [39].
• In vivo the tumor showed no evidence of differentiation by light microscopy, electron microscopy, and immunoperoxidase staining for myoglobin or skeletal muscle myosin [40].
• Processed lipoaspirate cells were placed in promyogenic conditions for up to 6 weeks, and the expression of the myogenic markers MyoD1 and myosin heavy chain was confirmed by using structure, histology, and reverse transcriptase-polymerase chain reaction [41].
• Molecular cloning and chromosomal localization of a gene coding for human cardiac myosin heavy-chain [42].

References