Phototransduction begins when a photon activates a rhodopsin molecule. Activated rhodopsin activates the G-protein transducin, which activates phosphodiesterase, leading to decreased cGMP concentration and closure of cyclic-nucleotide-gated channels. Termination of this process requires inactivation of rhodopsin and transducin. The former is mediated by arrestin, which separates the bleached ch...

Quenching of phototransduction in retinal rod cells involves phosphorylation of photoactivated rhodopsin by the enzyme rhodopsin kinase followed by binding of the protein arrestin. Although it has been proposed that the mechanism of arrestin quenching of visual transduction is via steric exclusion of transducin binding to phosphorylated light-activated rhodopsin (P-Rh*), direct evidence for thi...

Individual rhodopsin molecules have been resolved with atomic force microscopy as both monomers and various oligomeric organizations that are sensitively dependent upon the physical state of membranes and environmental conditions. In intact native disk membranes, rhodopsin molecules are observed as randomly dispersed monomers and small oligomers. In reconstituted rhodopsin-DPPC (dipalmitoylphos...

PURPOSE Following a previous study that demonstrated a correlation between rhodopsin stability and the severity of retinitis pigmentosa (RP), we investigated whether predictions of severity can be improved with a regional analysis of this correlation. The association between changes to the stability of the protein and the relative amount of rhodopsin reaching the plasma membrane was assessed. ...

Rhodopsin is a pigment in photoreceptor cells. Some rhodopsin mutations cause the protein to accumulate in the endoplasmic reticulum (ER), leading to photoreceptor degeneration. Although several mutations have been reported, how mutant rhodopsin is retained in the ER remains unclear. In this study, we identified Rer1p as a modulator of ER retention and rhodopsin trafficking. Loss of Rer1p incre...

Retinitis pigmentosa (RP) is a group of inherited diseases that primarily affect light‑sensitive rods and cones in the retina. Rhodopsin mutations, including the T17M mutation, are associated with the autosomal dominant form of retinitis pigmentosa (ADRP) and have been linked to abnormal protein folding. However, the molecular mechanisms underlying T17M rhodopsin‑induced retinal degeneration ar...

BACKGROUND P23H rhodopsin, a mutant rhodopsin, is known to aggregate and cause retinal degeneration. However, its effects on retinal pigment epithelial (RPE) cells are unknown. The purpose of this study was to determine the effect of P23H rhodopsin in RPE cells and further assess whether LEDGF(1-326), a protein devoid of heat shock elements of LEDGF, a cell survival factor, reduces P23H rhodops...

Two outstanding unknowns in the biology of photoreceptors are the molecular determinants of cell size, which is remarkably uniform among mammalian species, and the mechanisms of rod cell death associated with inherited neurodegenerative blinding diseases such as retinitis pigmentosa. We have addressed both questions by performing an in vivo titration with rhodopsin gene copies in genetically en...

PURPOSE To study mechanisms leading to photoreceptor degeneration in mouse models for autosomal dominant retinitis pigmentosa (adRP) based on the rhodopsin P23H mutation. METHODS Mice of a transgenic line expressing a rhodopsin triple mutant, V20G, P23H, and P27L (GHL), were mated with rhodopsin (rho) knockout mice. Littermates of various ages and genotypes (GHL+rho+/+, GHL+rho+/-, and GHL+rh...

Rhodopsin is palmitylated at two cysteine residues in its carboxyl terminal region. We have looked at the effects of palmitylation on the molecular interactions formed by rhodopsin using single-molecule force spectroscopy and the function of rhodopsin using both in vitro and in vivo approaches. A knockin mouse model expressing palmitate-deficient rhodopsin was used for live animal in vivo studi...