Myo5a

Summary

Gene Symbol: Myo5a
Description: myosin VA
Alias: 9630007J19Rik, AI413174, AI661011, Dbv, MVa, Myo5, MyoVA, Sev-1, d-120J, flail, flr, unconventional myosin-Va, dilute lethal-20J protein, dilute myosin heavy chain, non-muscle, flailer, myosin-Va
Species: mouse
Products:     Myo5a

Top Publications

  1. Wu X, Bowers B, Wei Q, Kocher B, Hammer J. Myosin V associates with melanosomes in mouse melanocytes: evidence that myosin V is an organelle motor. J Cell Sci. 1997;110 ( Pt 7):847-59 pubmed
  2. Reck Peterson S, Provance D, Mooseker M, Mercer J. Class V myosins. Biochim Biophys Acta. 2000;1496:36-51 pubmed
  3. Burgess S, Walker M, Wang F, Sellers J, White H, Knight P, et al. The prepower stroke conformation of myosin V. J Cell Biol. 2002;159:983-91 pubmed
    ..The microscopy shows that most of the walking stride is produced by changes in lever angle brought about by converter movement, but is augmented by distortion produced by thermal energy. ..
  4. Nascimento A, Amaral R, Bizario J, Larson R, Espreafico E. Subcellular localization of myosin-V in the B16 melanoma cells, a wild-type cell line for the dilute gene. Mol Biol Cell. 1997;8:1971-88 pubmed
  5. Schnell E, Nicoll R. Hippocampal synaptic transmission and plasticity are preserved in myosin Va mutant mice. J Neurophysiol. 2001;85:1498-501 pubmed
    Recent studies have identified myosin Va as an organelle motor that may have important functions in neurons...
  6. Moore K, Swing D, Rinchik E, Mucenski M, Buchberg A, Copeland N, et al. The murine dilute suppressor gene dsu suppresses the coat-color phenotype of three pigment mutations that alter melanocyte morphology, d, ash and ln. Genetics. 1988;119:933-41 pubmed
    ..These studies provide new insights into the mechanism of action of dsu and into the interrelationships between members of a family of pigment genes. ..
  7. Yoshizaki T, Imamura T, Babendure J, Lu J, Sonoda N, Olefsky J. Myosin 5a is an insulin-stimulated Akt2 (protein kinase Bbeta) substrate modulating GLUT4 vesicle translocation. Mol Cell Biol. 2007;27:5172-83 pubmed
  8. Volkmann N, Liu H, Hazelwood L, Krementsova E, Lowey S, Trybus K, et al. The structural basis of myosin V processive movement as revealed by electron cryomicroscopy. Mol Cell. 2005;19:595-605 pubmed
    ..Our findings reveal how the structural elements of myosin V work together to allow myosin V to step along actin for multiple ATPase cycles without dissociating. ..
  9. Ramalho J, Lopes V, Tarafder A, Seabra M, Hume A. Myrip uses distinct domains in the cellular activation of myosin VA and myosin VIIA in melanosome transport. Pigment Cell Melanoma Res. 2009;22:461-73 pubmed publisher
    ..Myrip also binds MyosinVa (MyoVa) in vitro however it is unclear whether this interaction is of sufficient affinity to be physiologically relevant...

More Information

Publications62

  1. Hume A, Collinson L, Hopkins C, Strom M, Barral D, Bossi G, et al. The leaden gene product is required with Rab27a to recruit myosin Va to melanosomes in melanocytes. Traffic. 2002;3:193-202 pubmed
    ..Melanocytes from Griscelli syndrome patients and respective murine models ashen (Rab27a mutant), dilute (myosin Va mutant), and leaden exhibit perinuclear clustering of melanosomes...
  2. Takagishi Y, Hashimoto K, Kayahara T, Watanabe M, Otsuka H, Mizoguchi A, et al. Diminished climbing fiber innervation of Purkinje cells in the cerebellum of myosin Va mutant mice and rats. Dev Neurobiol. 2007;67:909-23 pubmed
    b>Myosin Va is an actin-based molecular motor that is involved in organelle transport and membrane trafficking...
  3. Yoshimura A, Fujii R, Watanabe Y, Okabe S, Fukui K, Takumi T. Myosin-Va facilitates the accumulation of mRNA/protein complex in dendritic spines. Curr Biol. 2006;16:2345-51 pubmed
    ..Our results demonstrate that myosin-Va facilitates the transport of TLS-containing mRNP complexes in spines and may function in synaptic plasticity through Ca2+ signaling. ..
  4. Fukuda M, Kuroda T. Slac2-c (synaptotagmin-like protein homologue lacking C2 domains-c), a novel linker protein that interacts with Rab27, myosin Va/VIIa, and actin. J Biol Chem. 2002;277:43096-103 pubmed
    ..lacking C2 domains-a)/melanophilin is a melanosome-associated protein that links Rab27A on melanosomes with myosin Va, an actin-based motor protein, and formation of the tripartite protein complex (Rab27A.Slac2-a...
  5. Moore J, Krementsova E, Trybus K, Warshaw D. Myosin V exhibits a high duty cycle and large unitary displacement. J Cell Biol. 2001;155:625-35 pubmed
    ..The second step is characterized by an increased displacement variance, suggesting a model for how the two heads of myosin V function in processive motion. ..
  6. Hume A, Ushakov D, Tarafder A, Ferenczi M, Seabra M. Rab27a and MyoVa are the primary Mlph interactors regulating melanosome transport in melanocytes. J Cell Sci. 2007;120:3111-22 pubmed
    ..Melanophilin (Mlph) is a Rab27a- and myosin Va (MyoVa)-binding protein that regulates this process...
  7. Hodge T, Cope M. A myosin family tree. J Cell Sci. 2000;113 Pt 19:3353-4 pubmed
  8. Wu X, Rao K, Zhang H, Wang F, Sellers J, Matesic L, et al. Identification of an organelle receptor for myosin-Va. Nat Cell Biol. 2002;4:271-8 pubmed
  9. Miyata M, Finch E, Khiroug L, Hashimoto K, Hayasaka S, Oda S, et al. Local calcium release in dendritic spines required for long-term synaptic depression. Neuron. 2000;28:233-44 pubmed
    ..Our results reveal that IP3 must release Ca2+ locally in the dendritic spines to produce LTD and indicate that one function of dendritic spines is to target IP3-mediated Ca2+ release to the proper subcellular domain. ..
  10. Pastural E, Barrat F, Dufourcq Lagelouse R, Certain S, Sanal O, Jabado N, et al. Griscelli disease maps to chromosome 15q21 and is associated with mutations in the myosin-Va gene. Nat Genet. 1997;16:289-92 pubmed
    ..Here we report that the Griscelli disease locus co-localizes on chromosome 15q21 with the myosin-Va gene, MYO5a, and that mutations of this gene occur in two patients with the disease...
  11. O Sullivan T, Wu X, Rachel R, Huang J, Swing D, Matesic L, et al. dsu functions in a MYO5A-independent pathway to suppress the coat color of dilute mice. Proc Natl Acad Sci U S A. 2004;101:16831-6 pubmed
    b>MYO5A is a major actin-based vesicle transport motor that binds to one of its cargos, the melanosome, by means of a RAB27A/MLPH receptor...
  12. Mercer J, Seperack P, Strobel M, Copeland N, Jenkins N. Novel myosin heavy chain encoded by murine dilute coat colour locus. Nature. 1991;349:709-13 pubmed
    ..These results suggest an important role for the dilute gene product in the elaboration, maintenance, or function of cellular processes of melanocytes and neurons. ..
  13. Nagy N, Sakamoto T, Takacs B, Gyimesi M, Hazai E, Bikadi Z, et al. Functional adaptation of the switch-2 nucleotide sensor enables rapid processive translocation by myosin-5. FASEB J. 2010;24:4480-90 pubmed publisher
    ..The class-specific variation of switch-2 in various NTPase superfamilies indicates its general role in the kinetic tuning of Mg(2+)-dependent nucleotide exchange. ..
  14. Wu X, Masedunskas A, Weigert R, Copeland N, Jenkins N, Hammer J. Melanoregulin regulates a shedding mechanism that drives melanosome transfer from melanocytes to keratinocytes. Proc Natl Acad Sci U S A. 2012;109:E2101-9 pubmed publisher
    ..Tip accumulation of melanosomes requires myosin Va, because melanosomes concentrate in the center of melanocytes from myosin Va-null (dilute) mice...
  15. Liakath Ali K, Vancollie V, Heath E, Smedley D, Estabel J, Sunter D, et al. Novel skin phenotypes revealed by a genome-wide mouse reverse genetic screen. Nat Commun. 2014;5:3540 pubmed publisher
    ..In-depth analysis of three mutants, Krt76, Myo5a (a model of human Griscelli syndrome) and Mysm1, provides validation of the screen...
  16. Strobel M, Seperack P, Copeland N, Jenkins N. Molecular analysis of two mouse dilute locus deletion mutations: spontaneous dilute lethal20J and radiation-induced dilute prenatal lethal Aa2 alleles. Mol Cell Biol. 1990;10:501-9 pubmed
    ..Initial characterization of this new gene suggests that it may represent the genetically defined pl-3 functional unit. ..
  17. Takagishi Y, Oda S, Hayasaka S, Dekker Ohno K, Shikata T, Inouye M, et al. The dilute-lethal (dl) gene attacks a Ca2+ store in the dendritic spine of Purkinje cells in mice. Neurosci Lett. 1996;215:169-72 pubmed
  18. Fukuda M, Kuroda T. Missense mutations in the globular tail of myosin-Va in dilute mice partially impair binding of Slac2-a/melanophilin. J Cell Sci. 2004;117:583-91 pubmed
    ..On the basis of our findings, we propose that myosin-Va interacts with Slac2-a.Rab27A complex on the melanosome via two distinct domains, both of which are essential for melanosome transport in melanocytes. ..
  19. Sakamoto T, Webb M, Forgacs E, White H, Sellers J. Direct observation of the mechanochemical coupling in myosin Va during processive movement. Nature. 2008;455:128-32 pubmed publisher
    b>Myosin Va transports intracellular cargoes along actin filaments in cells...
  20. Mermall V, Post P, Mooseker M. Unconventional myosins in cell movement, membrane traffic, and signal transduction. Science. 1998;279:527-33 pubmed
    ..The task at hand is to decipher how the multitude of myosins function at both the molecular and cellular level-a task facilitated by our understanding of myosin structure and function in muscle. ..
  21. Provance D, Wei M, Ipe V, Mercer J. Cultured melanocytes from dilute mutant mice exhibit dendritic morphology and altered melanosome distribution. Proc Natl Acad Sci U S A. 1996;93:14554-8 pubmed
    ..These experiments show that the dilute myosin is necessary for the localization of melanosomes, either by active transport or tethering. ..
  22. Jones J, Huang J, Mermall V, Hamilton B, Mooseker M, Escayg A, et al. The mouse neurological mutant flailer expresses a novel hybrid gene derived by exon shuffling between Gnb5 and Myo5a. Hum Mol Genet. 2000;9:821-8 pubmed
    ..Here we show that the mouse neurological mutation flailer (flr) expresses a novel gene that combines the promoter and first two exons of guanine nucleotide binding protein ..
  23. Libby R, Lillo C, Kitamoto J, Williams D, Steel K. Myosin Va is required for normal photoreceptor synaptic activity. J Cell Sci. 2004;117:4509-15 pubmed
    b>Myosin Va is an actin-based motor molecule, one of a large family of unconventional myosins...
  24. Varadi A, Tsuboi T, Rutter G. Myosin Va transports dense core secretory vesicles in pancreatic MIN6 beta-cells. Mol Biol Cell. 2005;16:2670-80 pubmed
    ..Here, we demonstrate colocalization of myosin Va (MyoVa) with insulin in pancreatic beta-cells and show that MyoVa copurifies with insulin in density gradients ..
  25. Röder I, Petersen Y, Choi K, Witzemann V, Hammer J, Rudolf R. Role of Myosin Va in the plasticity of the vertebrate neuromuscular junction in vivo. PLoS ONE. 2008;3:e3871 pubmed publisher
    b>Myosin Va is a motor protein involved in vesicular transport and its absence leads to movement disorders in humans (Griscelli and Elejalde syndromes) and rodents (e.g. dilute lethal phenotype in mice)...
  26. Sweet H. Dilute suppressor, a new suppressor gene in the house mouse. J Hered. 1983;74:305-6 pubmed
    ..Dilute suppressor is located on chromosome 1 linked to isocitrate dehydrogenase (Idh-I) with 6.25 +/- 3.49 percent recombination, and is not linked to dilute, which is on chromosome 9. ..
  27. Seperack P, Mercer J, Strobel M, Copeland N, Jenkins N. Retroviral sequences located within an intron of the dilute gene alter dilute expression in a tissue-specific manner. EMBO J. 1995;14:2326-32 pubmed
    ..These findings have important implications for understanding the effects of viral sequences on mammalian gene expression. ..
  28. Engle L, Kennett R. Cloning, analysis, and chromosomal localization of myoxin (MYH12), the human homologue to the mouse dilute gene. Genomics. 1994;19:407-16 pubmed
    ..We report the isolation and sequencing of "myoxin" (MYH12), the human homologue of the mouse dilute gene, and its assignment to human chromosome 15. ..
  29. Huang J, Mermall V, Strobel M, Russell L, Mooseker M, Copeland N, et al. Molecular genetic dissection of mouse unconventional myosin-VA: tail region mutations. Genetics. 1998;148:1963-72 pubmed
    ..Ten of the mutations mapped to the MyoVA tail and are reported here...
  30. Yengo C, De La Cruz E, Safer D, Ostap E, Sweeney H. Kinetic characterization of the weak binding states of myosin V. Biochemistry. 2002;41:8508-17 pubmed
  31. Rao M, Engle L, Mohan P, Yuan A, Qiu D, Cataldo A, et al. Myosin Va binding to neurofilaments is essential for correct myosin Va distribution and transport and neurofilament density. J Cell Biol. 2002;159:279-90 pubmed
    ..Here, we show that a molecular motor protein, myosin Va, is present in high proportions in the cytoskeleton of mouse CNS and peripheral nerves...
  32. Provance D, James T, Mercer J. Melanophilin, the product of the leaden locus, is required for targeting of myosin-Va to melanosomes. Traffic. 2002;3:124-32 pubmed
    ..The loci have been renamed Rab27a, Myo5a, and Mlph for their gene products...
  33. Kad N, Trybus K, Warshaw D. Load and Pi control flux through the branched kinetic cycle of myosin V. J Biol Chem. 2008;283:17477-84 pubmed publisher
    ..Our model includes P(i) release prior to the most load-dependent step in the cycle, implying that P(i) release and load both act as checkpoints that control the flux through two parallel pathways. ..
  34. Hume A, Collinson L, Rapak A, Gomes A, Hopkins C, Seabra M. Rab27a regulates the peripheral distribution of melanosomes in melanocytes. J Cell Biol. 2001;152:795-808 pubmed
    ..by others in melanocytes derived from the ashen and dilute mutant mice, which bear mutations in the Rab27a and MyoVa loci, respectively...
  35. Jenkins N, Copeland N, Taylor B, Lee B. Dilute (d) coat colour mutation of DBA/2J mice is associated with the site of integration of an ecotropic MuLV genome. Nature. 1981;293:370-4 pubmed
  36. Hume A, Tarafder A, Ramalho J, Sviderskaya E, Seabra M. A coiled-coil domain of melanophilin is essential for Myosin Va recruitment and melanosome transport in melanocytes. Mol Biol Cell. 2006;17:4720-35 pubmed
    ..Mlph is proposed to be a modular protein binding the melanosome-associated protein Rab27a, Myosin Va (MyoVa), actin, and microtubule end-binding protein (EB1), via distinct N-terminal Rab27a-binding domain (R27BD),..
  37. Strom M, Hume A, Tarafder A, Barkagianni E, Seabra M. A family of Rab27-binding proteins. Melanophilin links Rab27a and myosin Va function in melanosome transport. J Biol Chem. 2002;277:25423-30 pubmed
    ..We also show that melanophilin associates with Rab27a and myosin Va on melanosomes in melanocytes, and present evidence that a domain within the carboxyl-terminal region of ..
  38. Wang F, Thirumurugan K, Stafford W, Hammer J, Knight P, Sellers J. Regulated conformation of myosin V. J Biol Chem. 2004;279:2333-6 pubmed
    ..These data suggest that interaction between the motor and cargo binding domains may be a general mechanism for shutting down motor protein activity and thereby regulating the active movement of vesicles in cells. ..
  39. Wagner W, Brenowitz S, Hammer J. Myosin-Va transports the endoplasmic reticulum into the dendritic spines of Purkinje neurons. Nat Cell Biol. 2011;13:40-8 pubmed publisher
    ..Purkinje neurons is required for cerebellar synaptic plasticity and is disrupted in animals with null mutations in Myo5a, the gene encoding myosin-Va...
  40. Moore K, Seperack P, Strobel M, Swing D, Copeland N, Jenkins N. Dilute suppressor dsu acts semidominantly to suppress the coat color phenotype of a deletion mutation, dl20J, of the murine dilute locus. Proc Natl Acad Sci U S A. 1988;85:8131-5 pubmed
    ..We also show that dsu is not, as originally reported, a recessive gene but is semidominantly inherited. Collectively, these results allow us to propose a mechanism for the suppressor activity of dsu. ..
  41. Petralia R, Wang Y, Sans N, Worley P, Hammer J, Wenthold R. Glutamate receptor targeting in the postsynaptic spine involves mechanisms that are independent of myosin Va. Eur J Neurosci. 2001;13:1722-32 pubmed
    ..These mutant mice lack myosin Va, which has been implicated in protein trafficking at synapses...
  42. Forgacs E, Sakamoto T, Cartwright S, Belknap B, Kovacs M, Toth J, et al. Switch 1 mutation S217A converts myosin V into a low duty ratio motor. J Biol Chem. 2009;284:2138-49 pubmed publisher
    We have determined the kinetic mechanism and motile properties of the switch 1 mutant S217A of myosin Va. Phosphate dissociation from myosin V-ADP-Pi (inorganic phosphate) and actomyosin V-ADP-Pi and the rate of the hydrolysis step (..
  43. Au J, Huang J. A tissue-specific exon of myosin Va is responsible for selective cargo binding in melanocytes. Cell Motil Cytoskeleton. 2002;53:89-102 pubmed
    Class V myosins are molecular motors used for intracellular transportation and organelle tethering. The mouse Myosin Va (MyoVa) is encoded by the dilute locus, which is alternatively spliced to generate several tissue specific isoforms...
  44. Alami N, Jung P, Brown A. Myosin Va increases the efficiency of neurofilament transport by decreasing the duration of long-term pauses. J Neurosci. 2009;29:6625-34 pubmed publisher
    ..transport of neurofilaments in cultured neurons from two different strains of dilute lethal mice, which lack myosin Va. To analyze the motile behavior, we tracked the movement of green fluorescent protein (GFP)-tagged ..
  45. Röder I, Choi K, Reischl M, Petersen Y, Diefenbacher M, Zaccolo M, et al. Myosin Va cooperates with PKA RIalpha to mediate maintenance of the endplate in vivo. Proc Natl Acad Sci U S A. 2010;107:2031-6 pubmed publisher
    ..We found that myosin Va cooperates with PKA on the postsynapse to maintain size and integrity of the synapse; this cooperation also ..
  46. Blankenhorn E, Douglas T. Location of the gene for Theta antigen in the mouse. J Hered. 1972;63:259-63 pubmed
  47. Varki A, Kornfeld S. An autosomal dominant gene regulates the extent of 9-O-acetylation of murine erythrocyte sialic acids. A probable explanation for the variation in capacity to activate the human alternate complement pathway. J Exp Med. 1980;152:532-44 pubmed
    ..By using recombinant inbred strains, we determined that this genetic locus is probably located on chromosome 9. The nature of the gene product remains unknown. ..
  48. Kingsley D, Jenkins N, Copeland N. A molecular genetic linkage map of mouse chromosome 9 with regional localizations for the Gsta, T3g, Ets-1 and Ldlr loci. Genetics. 1989;123:165-72 pubmed
    ..In addition, the close linkage detected between the dilute and Gsta loci suggests that the Gsta locus may be part of the dilute/short ear complex, one of the most extensively studied genetic regions of the mouse. ..
  49. Winterbourn C, Woolf F, Woolf L. Brain lipids of mice homozygous for the gene 'dilute lethal' (d). J Neurochem. 1971;18:1077-86 pubmed
  50. Baboolal T, Sakamoto T, Forgacs E, White H, Jackson S, Takagi Y, et al. The SAH domain extends the functional length of the myosin lever. Proc Natl Acad Sci U S A. 2009;106:22193-8 pubmed publisher
    ..can act as levers, we replaced four of the six calmodulin-binding IQ motifs in the levers of mouse myosin 5a (Myo5) with the putative SAH domain of Dictyostelium myosin MyoM of similar length...
  51. Avraham K, Hasson T, Steel K, Kingsley D, Russell L, Mooseker M, et al. The mouse Snell's waltzer deafness gene encodes an unconventional myosin required for structural integrity of inner ear hair cells. Nat Genet. 1995;11:369-75 pubmed
    ..The requirement for myosin VI in hearing makes this gene an excellent candidate for a human deafness disorder. ..
  52. Lu Z, Shen M, Cao Y, Zhang H, Yao L, Li X. Calmodulin bound to the first IQ motif is responsible for calcium-dependent regulation of myosin 5a. J Biol Chem. 2012;287:16530-40 pubmed publisher
    ..We propose that Ca(2+) induces a conformational change of the C-lobe of CaM in IQ1 and prevents interaction between the head and the tail, thus activating motor function...
  53. Rise M, Frankel W, Coffin J, Seyfried T. Genes for epilepsy mapped in the mouse. Science. 1991;253:669-73 pubmed
    ..The location of El-1 on distal chromosome 9 may allow identification of an epilepsy candidate gene in humans on the basis of conserved synteny with human chromosome 3. ..