Details

Autor(en) / Beteiligte

• Walsh, Tom
• Walsh, Vanessa
• Vreugde, Sarah
• Hertzano, Ronna
• Shahin, Hashem
• Haika, Smadar
• Lee, Ming K.
• Kanaan, Moien
• King, Mary-Claire
• Avraham, Karen B.

Titel

From Flies' Eyes to Our Ears: Mutations in a Human Class III Myosin Cause Progressive Nonsyndromic Hearing Loss DFNB30

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2002-05, Vol.99 (11), p.7518-7523

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2002

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Normal vision in Drosophila requires NINAC, a class III myosin. Class III myosins are hybrid motor-signaling molecules, with an N-terminal kinase domain, highly conserved head and neck domains, and a class III-specific tail domain. In Drosophila rhabdomeres, NINAC interacts with actin filaments and with a PDZ scaffolding protein to organize the phototransduction machinery into a signaling complex. Recessive null mutations in Drosophila NINAC delay termination of the photoreceptor response and lead to progressive retinal degeneration. Here, we show that normal hearing in humans requires myosin IIIA, the human homolog of NINAC. In an extended Israeli family, nonsyndromic progressive hearing loss is caused by three different recessive, loss-of-function mutations in myosin IIIA. Of 18 affected relatives in Family N, 7 are homozygous and 11 are compound heterozygous for pairs of mutant alleles. Expression of mammalian myosin IIIA is highly restricted, with the strongest expression in retina and cochlea. The involvement of homologous class III myosins in both Drosophila vision and human hearing is an evolutionary link between these sensory systems.