Disease relevance of mhcA

• To evaluate whether the Asn458Ile mutation was indeed responsible for the hearing impairment, a molecular model of myosin VIIA was built based on the known structure of the myosin II heavy chain from Dictyostelium discoideum [1].

High impact information on mhcA

• The mhcA- mutant of the amoebal stage of the slime mould Dictyostelium discoideum, in which the myosin II gene has been deleted, cannot cap surface particles but can crawl along the substratum [2].
• We present evidence that MHC is phosphorylated by MHC-PKC in the cell cortex which leads to myosin II dissociation from the cytoskeleton [3].
• The eukaryotic slime mold Dictyostelium discoideum has a single conventional myosin heavy chain gene (mhcA) [4].
• Myosin null mutants (mhcA- cells) were obtained after transformation with either of these plasmids [4].
• Myosin II filament assembly in Dictyostelium discoideum is regulated via phosphorylation of residues located in the carboxyl-terminal portion of the myosin II heavy chain (MHC) tail [5].

Biological context of mhcA

• One cell line (mhcA) was created by antisense RNA inactivation of the endogenous mRNA and the other (HMM) by insertional mutagenesis of the endogenous myosin gene [6].
• A mutation (mhcA1 in strain HMM) created by insertional gene inactivation was used to map the Dictyostelium discoideum myosin heavy chain gene (mhcA) to linkage group IV [7].
• The myosin heavy chain gene A, mhcA, from E. histolytica was identified by polymerase chain reaction [8].
• Here we report that elimination of MHC-PKC results in the abolishment of MHC phosphorylation in response to cAMP [9].
• Multiple myosin II heavy chain kinases: roles in filament assembly control and proper cytokinesis in Dictyostelium [5].

Anatomical context of mhcA

• We also found that cytoskeletal MHC showed only minor phosphorylation, the majority of the phosphorylated MHC being found in the cytosol [10].

Associations of mhcA with chemical compounds

• Myosin II heavy chain (MHC) specific protein kinase C (MHC-PKC), isolated from Dictyostelium discoideum, regulates myosin II assembly and localization in response to the chemoattractant cyclic AMP [11].
• Evidence of cyclic GMP may regulate the association of myosin II heavy chain with the cytoskeleton by inhibiting its phosphorylation [10].
• Conversion of the three mapped threonine phosphorylation sites in the myosin II heavy chain tail to alanines results in a mutant (3XALA) in Dictyostelium discoideum, which displays constitutive myosin overassembly in the cytoskeleton and increased cortical tension [12].

Regulatory relationships of mhcA

• The mhcA cells have negligible amounts of MHC A protein while the HMM cells express normal amounts of a fragment of the myosin heavy chain protein similar to heavy meromyosin (HMM) [6].

Other interactions of mhcA

• Mutants isolated in a similar screen suffered a disruption in the myosin II heavy chain gene, a protein known to be essential for cytokinesis and in a novel gene encoding a rho-like protein termed racE [Larochelle et al., 1996] [13].
• The rules and characteristics of nuclear behavior are demonstrated to be intact in two mutants affecting pseudopod formation, a myosin IB null mutant (myoB-) and a myosin II heavy chain phosphorylation mutant (3XALA) [14].

References