MOLECULAR-CLONING AND DOMAIN-STRUCTURE OF HUMAN MYOSIN-VIIA - THE GENE-PRODUCT DEFECTIVE IN USHER SYNDROME 1B

Myosin-VIIa is an unconventional myosin with relatively restricted exp ression. Cloned first from an intestinal epithelium cell line, it occu rs 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 c ause the shaker-1 phenotype in mice and Usher syndrome 1B in human, wh ich are characterized by deafness, lack of vestibular function, and (i n human) progressive retinal degeneration. Because the described cDNAs encode less than half of the protein predicted from immunoblots, we h ave cloned cDNAs encoding the rest of human myosin-VIIa. Two transcrip ts were found, one encoding the predicted 250-kDa protein and another encoding a shorter form. Both transcripts were found in highest abunda nce in testis, although the shorter transcript was much less abundant. Both could be detected in lymphocytes by RT-PCR, The myosin tail enco ded by the long transcript includes a long repeat of similar to 460 am ino acids. Each repeat contains a novel ''MyTH4'' domain similar to do mains in three other myosins, and a domain similar to the membrane-ass ociated portion of talin and other members of the band-4.1 family. (C) 1996 Academic Press, Inc.