Dependence on a retinophilin/myosin complex for stability of PKC and INAD and termination of phototransduction
Authors
Venkatachalam, KartikWasserman, David
Wang, Xiaoyue
Li, Ruoxia
Mills, Eric
Elsaesser, Rebecca
Li, Hong-Sheng
Montell, Craig
Document Type
Journal ArticlePublication Date
2010-08-25Keywords
AnimalsAnimals, Genetically Modified
Drosophila
Drosophila Proteins
Enzyme Stability
Eye Proteins
Light Signal Transduction
Myosin Heavy Chains
Myosins
Photic Stimulation
Protein Kinase C
Neuroscience and Neurobiology
Metadata
Show full item recordAbstract
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.Source
J Neurosci. 2010 Aug 25;30(34):11337-45. Link to article on publisher's siteDOI
10.1523/JNEUROSCI.2709-10.2010Permanent Link to this Item
http://hdl.handle.net/20.500.14038/37832PubMed ID
20739554Related Resources
Link to Article in PubMedRights
Copyright © 2010 the authors. Copyright of all material published in The Journal of Neuroscience remains with the authors. The authors grant the Society for Neuroscience an exclusive license to publish their work for the first 6 months. After 6 months the work becomes available to the public to copy, distribute, or display under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported license.ae974a485f413a2113503eed53cd6c53
10.1523/JNEUROSCI.2709-10.2010