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 microtuble doublets in the axonemes has been demonstrated in some RP cases, a type of axonemal defect also commonly seen in sperm flagella 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 alpha tubulin acetylation may be important in the normal function of cilia and flagellae and have reported on a human male subject who has rod dominant RP and a low level of acetylated tubulin, apparently due a low specific acetylation activity. Tubulin acetylation activity in bovine retina is associated with a cold-stable microtubule fraction in a multiprotein complex of about 300 kDa. A 48 kDa band in the complex was immunoreactive for rod photoreceptor arrestin; also, purified brain microtubules copolymerized with the isolated retinal acetylation complex contained arrestin. Ultrafiltration studies of the retinal acetylation complex showed retention of arrestin immunoreactivity by 100 kDa MWCO membranes except in the presence of high, dissociating NaCl concentrations. IRBP (interphotoreceptor retinoid binding protein) also copurified with the acetylation complex from retina. Arrestin and IRBP have been reported to translocate into the outer segment in response to light signals. In contrast, transducin, although colocalizing with microtubule-associated proteins, did not copurify with the tubulin acetylation complex. The results from the acetylation complex studies suggested that the complex may be acting in the translocation of some photoreceptor-specific proteins in response to a lights/on signal.
