title: Myr 7 is a novel myosin IX-RhoGAP expressed in rat brain.
abstract: Rho family GTPases are important regulators of neuronal morphology, but the proteins directly controlling their activity in neurons are still poorly defined. We report the identification of myr 7, a novel unconventional myosin IX-RhoGAP expressed in rat brain. Myr 7 is a multidomain protein related to myr 5, the first class IX myosin to be characterized. It exhibits a myosin head domain with an N-terminal extension and a large insertion at loop 2, an actin contact site and regulator of myosin ATPase rate. The myosin head domain is followed by a neck domain consisting of six unevenly spaced consecutive IQ motifs representing light chain binding sites. The tail domain contains a C6H2-zinc binding motif and a region that specifically stimulates the GTPase-activity of Rho followed by a short stretch predicted to adopt a coiled-coil structure. Five alternatively spliced regions, one in the 5'-noncoding region, two in the myosin head and two in the tail domain, were noted. Analysis of myr 7 and myr 5 expression in different tissues revealed that myr 7 is expressed at high levels in developing and adult brain tissue whereas myr 5 is expressed only at moderate levels in embryonic brain tissue and at even further reduced levels in adult brain tissue. Myr 5 is, however, highly expressed in lung, liver, spleen and testis. Myr 7 is expressed in all brain regions and is localized in the cytoplasm of cell bodies, dendrites and axons. Myr 5 exhibits an overlapping, but not identical cellular distribution. Finally, a myr 7 fusion protein encompassing the GAP domain specifically activates the GTPase-activity of Rho in vitro, and overexpression of myr 7 in HtTA1-HeLa cells leads to inactivation of Rho in vivo. These results are compatible with a role for myr 7 (and myr 5) in regulating Rho activity in neurons and hence in regulating neuronal morphology and function.
authors.affiliation: Friedrich-Miescher Laboratorium in the Max-Planck Society,Tübingen, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Chieregatti
authors.forename: A
authors.initials: A
authors.lastname: Gärtner
authors.forename: H E
authors.initials: HE
authors.lastname: Stöffler
authors.forename: M
authors.initials: M
authors.lastname: Bähler
mesh_terms: D000311:Adrenal Glands / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000201:enzymology / Q000378:metabolism*; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004622:Embryo, Mammalian; D004789:Enzyme Activation; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D020690:GTPase-Activating Proteins; D018507:Gene Expression Regulation, Developmental; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008969:Molecular Sequence Data; D009218:Myosins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D009928:Organ Specificity; D051381:Rats; D017208:Rats, Wistar; D013737:Testis / Q000378:metabolism; D020741:rho GTP-Binding Proteins
chemical_list: D020690:GTPase-Activating Proteins; C503808:Myo1e protein, rat; C113469:myosin IXB; C085379:rho GTPase-activating protein; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D009218:Myosins; D020741:rho GTP-Binding Proteins