Dependence on a retinophilin/myosin complex for stability of PKC and INAD and termination of phototransduction

TitleDependence on a retinophilin/myosin complex for stability of PKC and INAD and termination of phototransduction
Publication TypeJournal Article
Year of Publication2010
AuthorsVenkatachalam K, Wasserman D, Wang X, Li R, Mills E, Elsaesser R, Li H-S, Montell C
JournalJ Neurosci
Volume30
Pagination11337-45
Date Published08/2010
ISSN1529-2401
KeywordsAnimals, Animals, Genetically Modified, Drosophila, Drosophila Proteins, Enzyme Stability, Eye Proteins, Light Signal Transduction, Myosin Heavy Chains, Myosins, Photic Stimulation, Protein Kinase C
Abstract

Normal termination of signaling is essential to reset signaling cascades, especially those such as phototransduction that are turned on and off with great rapidity. Genetic approaches in Drosophila led to the identification of several proteins required for termination, including protein kinase C (PKC), NINAC (neither inactivation nor afterpotential C) p174, which consists of fused protein kinase and myosin domains, and a PDZ (postsynaptic density-95/Discs Large/zona occludens-1) scaffold protein, INAD (inactivation no afterpotential D). Here, we describe a mutation affecting a poorly characterized but evolutionarily conserved protein, Retinophilin (Retin), which is expressed primarily in the phototransducing compartment of photoreceptor cells, the rhabdomeres. Retin and NINAC formed a complex and were mutually dependent on each other for expression. Loss of retin resulted in an age-dependent impairment in termination of phototransduction. Mutations that affect termination of the photoresponse typically lead to a reduction in levels of the major rhodopsin (Rh1) to attenuate signaling. Consistent with the slower termination in retin(1), the mutant photoreceptor cells exhibited increased endocytosis of Rh1 and a decline in Rh1 protein. The slower termination in retin(1) was a consequence of a cascade of defects, which began with the reduction in NINAC p174 levels. The diminished p174 concentration caused a decrease in INAD. Because PKC requires interaction with INAD for protein stability, this leads to reduction in PKC levels. The decline in PKC was age dependent and paralleled the onset of the termination phenotype in retin(1) mutant flies. We conclude that the slower termination of the photoresponse in retin(1) resulted from a requirement for the Retin/NINAC complex for stability of INAD and PKC.

DOI10.1523/JNEUROSCI.2709-10.2010
Alternate JournalJ. Neurosci.
PubMed ID20739554
PubMed Central IDPMC2943201
Grant ListEY08117 / EY / NEI NIH HHS / United States
R01 AG022508 / AG / NIA NIH HHS / United States
R01 EY008117-23 / EY / NEI NIH HHS / United States