Disease relevance of Myh10

• Approximately 65% of the NMHC-B-/- embryos died prior to birth, and those that were born suffered from congestive heart failure and died during the first day [1].
• Preformed neurites in mouse Neuro-2A neuroblastoma cells undergo immediate retraction when exposed to isoform-specific antisense oligonucleotides that suppress myosin IIB expression, ruling out myosin IIB as the retraction motor [2].

High impact information on Myh10

• These data on B(DeltaI)/B(DeltaI) and B(DeltaI)/B(-) mice demonstrate a gene dosage effect of the amount of NMHC-B on the severity and time of onset of the defects in the heart and brain [3].
• Complete ablation of nonmuscle myosin heavy chain II-B (NMHC-B) in mice resulted in cardiac and brain defects that were lethal during embryonic development or on the day of birth [3].
• By contrast, the myosin IIA isoform is shown to be expressed constitutively both before and during neurite outgrowth and throughout exposure to myosin IIB antisense oligodeoxyribonucleotides [4].
• The increase in size of the cardiac myocytes was seen as early as embryonic day 12.5 (4.5 +/- 0.2 micron for NMHC-B+/+ and B+/- vs. 7. 2 +/- 0.6 micron for NMHC-B-/- mice (P < 0.01)) [1].
• The absence of NMHC-B resulted in a significant increase in the transverse diameters of the cardiac myocytes from 7.8 +/- 1.8 micron (right ventricle) and 7.8 +/- 1.3 micron (left ventricle) in NMHC-B+/+ and B+/- mice to 14.7 +/- 1.1 micron and 13.8 +/- 2.3 micron, respectively, in NMHC-B-/- mice (in both cases, P < 0.001) [1].

Biological context of Myh10

• However, unlike neuron-specific expression of the NMHC II-B insert, the NMHC II-C inserted isoform has widespread tissue distribution [5].
• Ablation and mutation of nonmuscle myosin heavy chain II-B results in a defect in cardiac myocyte cytokinesis [6].
• An increase in binucleation and cell size is also found in hypomorphic, homozygous mice harboring a single amino acid mutation (R709C) in the gene encoding NMHC II-B [6].
• Some of the hearts of NMHC-B-/- mice showed evidence for up-regulation of NMHC-A protein [1].
• Knockdown of myosin IIB suppressed wound-induced exocytosis and the membrane resealing process [7].

Anatomical context of Myh10

• NMHC II-C contains an alternatively spliced exon of 24 nucleotides in loop I at a location analogous to where a spliced exon appears in NMHC II-B and in the smooth muscle myosin heavy chain [5].
• In contrast to most cells, cardiac myocytes lack NMHC II-A, and ablation of NMHC II-B results in a heart with 70% fewer myocytes at embryonic day 14.5 (E14.5) than control mice (B+/B- and B+/B+) [6].
• Six of seven NMHC-B-/- newborn mice analyzed by serial sectioning also showed structural cardiac defects, including a ventricular septal defect, an aortic root that either straddled the defect or originated from the right ventricle, and muscular obstruction to right ventricular outflow [1].
• The interaction of NMHCB with PBX was verified by coimmunoprecipitation, and immunofluorescence staining revealed colocalization of NMHCB with cytoplasmic PBX in the mouse embryo distal limb bud [8].
• Nonmuscle myosin IIb is involved in the guidance of fibroblast migration [9].

Associations of Myh10 with chemical compounds

• Myosin IIB null cells displayed multiple unstable and disorganized protrusions, although they were still able to generate a large fraction of traction forces when cultured on flexible polyacrylamide substrates [9].
• In contrast, Y27632 did not inhibit outgrowth, a myosin IIB-dependent process [2].
• The clonal transfectants, expressing muristerone A-induced nmMHC-B, displayed a slightly flatter morphology and reached to a lower saturation density compared to the parental transformed cells [10].

Physical interactions of Myh10

• Immunoblotting with this antibody revealed that drebrin-binding cytoskeleton contains this myosin IIB-like immunreactivity [11].

Regulatory relationships of Myh10

• These data suggest that both myosin IIA and IIB normally contribute to retrograde flow and the properties of the flow are strongly influenced by myosin IIB because of its location and abundance [12].
• These effects of LPA on MTs and myosin IIB were blocked by pretreatment with inhibitors of the actomyosin and Rho pathways (cytochalasin D, blebbistatin, and Y27632), but not by an MT stabilizer (taxol), whereas taxol inhibited neurite retraction and MT depolymerization induced by nocodazole [13].
• Homeobox protein Hex induces SMemb/nonmuscle myosin heavy chain-B gene expression through the cAMP-responsive element [14].

Other interactions of Myh10

• We have addressed the function of one of the isoforms of myosin II, myosin IIB, by analyzing the movement and mechanical characteristics of fibroblasts where this protein has been ablated by gene disruption [9].
• Ablation of nonmuscle myosin heavy chain II-B (NMHC-B) in mice results in severe hydrocephalus with enlargement of the lateral and third ventricles [15].
• Non-muscle myosin IIB-like immunoreactivity is present at the drebrin-binding cytoskeleton in neurons [11].
• These results are consistent with increased production of ROS accelerating the switch from the contractile to the synthetic phenotype, characterized by increases in proliferation, migration, and expression of TM4 and SMemb and decreased alpha-actin [16].

Analytical, diagnostic and therapeutic context of Myh10

• Conversely, the microinjection of myosin IIB antibody blocks microfilament-directed chromosome scattering in Colcemid-treated mature oocytes, suggesting a role in mediating chromosome-cortical actomyosin interactions [17].
• Using confocal microscopy of neuromuscular junction preparations colabelled for myosin II isoforms and nerve terminal or muscle endplate markers, we demonstrate that both myosin IIA and myosin IIB are localized in nerve terminals [18].
• Immunohistochemistry using MAb G650 demonstrated that this myosin IIB-like immunreactivity can be detected in the neuronal cell bodies and their apical dendrites, where drebrin is hardly detected [11].

References