Molecular cloning and domain structure of human myosin-VIIa, the gene product defective in Usher syndrome 1B.
نویسندگان
چکیده
Myosin-VIIa is an unconventional myosin with relatively restricted expression. Cloned first from an intestinal epithelium cell line, it occurs most notably in the testis, in the receptor cells of the inner ear, and in the pigment epithelium of the retina. Defects in myosin-VIIa cause the shaker-1 phenotype in mice and Usher syndrome 1B in human, which are characterized by deafness, lack of vestibular function, and (in human) progressive retinal degeneration. Because the described cDNAs encode less than half of the protein predicted from immunoblots, we have cloned cDNAs encoding the rest of human myosin-VIIa. Two transcripts were found, one encoding the predicted 250-kDa protein and another encoding a shorter form. Both transcripts were found in highest abundance in testis, although the shorter transcript was much less abundant. Both could be detected in lymphocytes by RT-PCR. The myosin tail encoded by the long transcript includes a long repeat of approximately 460 amino acids. Each repeat contains a novel "MyTH4" domain similar to domains in three other myosins, and a domain similar to the membrane-associated portion of talin and other members of the band-4.1 family.
منابع مشابه
Myosin VIIa, the product of the Usher 1B syndrome gene, is concentrated in the connecting cilia of photoreceptor cells.
Usher syndrome is the most common form of combined deafness and blindness. The gene that is defective in Usher syndrome 1B (USH1B) encodes for an unconventional myosin, myosin VIIa. To understand the cellular function of myosin VIIa and why defects in it lead to USH1B, it is essential to determine the precise cellular and subcellular localization of the protein. We investigated the distribution...
متن کاملHuman Usher 1B/mouse shaker-1: the retinal phenotype discrepancy explained by the presence/absence of myosin VIIA in the photoreceptor cells.
Usher syndrome type 1 (USH1) associates severe congenital deafness, vestibular dysfunction and progressive retinitis pigmentosa leading to blindness. The gene encoding myosin VIIA is responsible for USH1B. Mutations in the murine orthologous gene lead to the shaker-1 phenotype, which manifests cochlear and vestibular dysfunction, without any retinal defect. To address this phenotypic discrepanc...
متن کاملMyosin VIIa as a common component of cilia and microvilli.
The distribution of myosin VIIa, which is defective or absent in Usher syndrome 1B, was studied in a variety of tissues by immunomicroscopy. The primary aim was to determine whether this putative actin-based mechanoenzyme is a common component of cilia. Previously, it has been proposed that defective ciliary function might be the basis of some forms of Usher syndrome. Myosin VIIa was detected i...
متن کاملThe cellular function of the usher gene product myosin VIIa is specified by its ligands.
Defects in myosin VIIa are responsible for Usher Syndrome 1B (Weil et al., 1995). Human Usher syndrome (USH), named after the British ophthalmologist Charles Usher (Usher, 1914), is the most common hereditary form of combined blindand deafness (≈ 50 % of cases in the developed countries). USH designates a group of clinically and genetically heterogeneous disorders with hearing loss and retiniti...
متن کاملInteractions in the network of Usher syndrome type 1 proteins.
Defects in myosin VIIa, harmonin (a PDZ domain protein), cadherin 23, protocadherin 15 and sans (a putative scaffolding protein), underlie five forms of Usher syndrome type I (USH1). Mouse mutants for all these proteins exhibit disorganization of their hair bundle, which is the mechanotransduction receptive structure of the inner ear sensory cells, the cochlear and vestibular hair cells. We hav...
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عنوان ژورنال:
- Genomics
دوره 36 3 شماره
صفحات -
تاریخ انتشار 1996