A novel form of the G protein beta subunit G beta(5) is specifically expressed in the vertebrate retina

The G protein beta subunit, G beta(5), is predominantly expressed in the central nervous system. In rodent brain, G beta(5) is expressed as a protein with an apparent molecular mass of 39,000 daltons (39 kDa). We have identified an additional G beta(5) immunoreactive protein of apparent size 44 kDa in the vertebrate retina, Molecular cloning and sequencing of polymerase chain reaction products revealed that the cDNA encoding the larger species of G beta(5) (G beta(5L)) was identical to the shorter form with the addition of 126 base pairs of 5' DNA sequence potentially encoding an in-frame 42-amino acid extension. Sequencing of mouse G beta(5) genomic clones demonstrated that the 126-base pair of retinal-specific coding material is derived hom a hitherto undetected 5' exon. During sucrose density gradient fractionation of bovine retinas, the 44-kDa G beta(5L) protein co-purified with rod outer segment membranes. Incubation of rod outer segment membranes with the nonhydrolyzable guanine nucleotide, GTP gamma S (guanosine 5'-3-O-(thio)triphosphate), which released the G beta subunit of transducin (G beta(1)), failed to remove G beta(5L). The 39-kDa G beta(5) protein displayed differential association with retinal and brain membranes. In the retina, G beta(5) was present as a soluble protein and was undetectable in the membrane fraction, whereas in the brain approximately 70% of G beta(5) was associated with cellular membranes. In transient COS-7 cell expression experiments, G beta(5L) formed functional G beta gamma dimers and G alpha beta gamma heterotrimers, and activated phosphoinositide-specific phospholipase C beta(2) in a manner indistinguishable from the 39-kDa G beta(2) protein. The cloning of the retinal-specific G beta(5L) cDNA suggests the existence of potentially novel G protein-mediated signaling cascades in photoreception.