Cytoskeletal abnormalities may underlie some forms of retinitis pigmentosa (RP), particularly those occurring in concert with other sensory problems such as deafness. A high incidence of cilia and flagella with missing microtubule doublets in the axonemes has been demonstrated in some RP cases, a type of axonemal defect also commonly seen in men with dyskinetic cilia syndrome. One of the invariant characteristics of axonemal microtubules (as well as the stable microtubules of axons) is that the alpha tubulin is acetylated. Therefore, we hypothesized that these post-translational modifications may be important in the normal function of cilia and flagellae and have reported on a human male subject who has rod dominant RP, delayed transmission in his auditory nerves, dyskinetic cilia syndrome, and temporal lobe seizure disorder. He has a low level of acetylated tubulin, apparently due to a low specific acetylation activity. Because very little is known about the tubulin acetylation activity, inquiries are being made into its basic structure and function using bovine retina. The activity is associated with the stable microtubule fraction in a complex of about 300 kDa, which showed several bands ranging between 40 kDa and 150 kDa on SDS-PAGE. Copolymerization of the complex from retina with purified brain microtubules contained rod photoreceptor arrestin. Interphotoreceptor retinoid-binding protein (IRBP) and alpha transducin have also been found in the acetylation complex from retina. There are two bands showing kinesin motor domain immunoreactivity, but these have not yet been characterized. Arrestin, IRBP, and transducin have been reported to be moved into the outer segment in response to light/dark signals. The results from the acetylation complex studies suggested that the complex may be acting in the translocation of these proteins.
