Novel myosin heavy chain encoded by murine dilute coat colour locus

Abstract

Hundreds of murine dilute mutations have been identified and analysed, making dilute one of the best genetically characterized of all mammalian loci. The recessive dilute (d) coat colour mutation carried by many inbred strains of mice produces a lightening of coat colour, caused by an abnormal adendritic melanocyte morphology that results in an uneven release of pigment granules into the developing hair shaft. Most dilute alleles (dilute-lethal) also produce a neurological defect, characterized by convulsions and opisthotonus, apparent at 8-10 days of age and continuing until the death of the animal at 2-3 weeks of age. The discovery that the original dilute allele (now termed dilute-viral or dV) is the result of the integration of an ecotropic murine leukaemia provirus has allowed the cloning of genomic DNA and in this study complementary DNA, from the dilute locus. The predicted dilute amino-acid sequence indicates that dilute encodes a novel type of myosin heavy chain, with a tail, or C-terminal, region that has elements of both type II (alpha-helical coiled-coil) and type I (non-coiled-coil) myosin heavy chains. Dilute transcripts are differentially expressed in both embryonic and adult tissues and are very abundant in neurons of the central nervous system, cephalic ganglia, and spinal ganglia. These results suggest an important role for the dilute gene product in the elaboration, maintenance, or function of cellular processes of melanocytes and neurons.

Immunohistochemical localization of myosin va in the adult rat brain

“…The expression of MVa is deficient in dilute mice (Mercer et al, 1991) and dilute-opisthotonus rats (Futaki et al, 2000). Both mutants present post-natal seizures and die within 3 weeks after birth.…”

“…Mammalian brain is a rich source of MVa, from which it has been purified and biochemically characterized (Espíndola et al, 1992;Espreafico et al, 1992;Cheney et al, 1993;Nascimento et al, 1996;Tauhata et al, 2001). The expression of MVa is deficient in dilute mice (Mercer et al, 1991) and diluteopisthotonus rats (Futaki et al, 2000), both of which present seizures soon after birth and die within the third post-natal week. The specific dysfunction that leads to the convulsions and post-natal death in these animals is not known.…”

“…MVa is broadly distributed in many brain regions in the mouse (Mercer et al, 1991) although strikingly intense labeling has been reported in specific cell types, such as Purkinje cells of the cerebellum (Espíndola et al, 1992;Espreafico et al, 1992), the outer plexiform layer of the retina (Schlamp and Williams, 1996) and a subset of neurons in the myenteric ganglia (Drengk et al, 2000).…”

Myosin-Va Regulates Exocytosis through the Submicromolar Ca2+-dependent Binding of Syntaxin-1A

“…Myosin-V, a processive molecular motor, conveys vesicles and other organelles along F-actin (Mercer et al, 1991;Espreafico et al, 1992;Cheney et al, 1993;Reck-Peterson et al, 2000;Vale, 2003). This unconventional myosin is a member of the class-V myosins, which are expressed in all eukaryotic species from yeast to mammals (Reck-Peterson et al, 2000;Matsui, 2003;Vale, 2003).…”

Mouse coat color mutations: From fancy mice to functional genomics

“…The bidirectional microtubule-based movements between the center of the cell and its periphery still take place in mutant melanocytes, but a failure in melanosome capture at the periphery results in their accumulation at the center (Wu et al, 1998). The d, ash, and ln loci encode for the Myosin Va, Rab27a and Melanophilin proteins, respectively (Mercer et al, 1991;Wilson et al, 2000;Matesic et al, 2001). Myosin Va is an actin-based motor protein that contains an N-terminal motor domain that binds to actin and generates force by hydrolyzing ATP, and a C-terminal domain that interacts with the cargo (Fig.…”