Prolonged Gq activity triggers fly rhodopsin endocytosis and degradation, and reduces photoreceptor sensitivity

Abstract

Rapid deactivation of the Drosophila light receptor rhodopsin, through a visual arrestin Arr2 and a pathway that involves a transcription factor dCAMTA, is required for timely termination of light responses in the photoreceptor neuron. Here we report that this process is also critical for maintenance of the photoreceptor sensitivity. In both dCAMTA- and arr2-mutant flies, the endocytosis of the major rhodopsin Rh1 was dramatically increased, which was mediated by a G(q) protein that signals downstream of rhodopsin in the visual transduction pathway. Consequently, the Rh1 level was downregulated and the photoreceptor became less sensitive to light. Remarkably, the G(q)-stimulated Rh1 endocytosis does not require phospholipase C, a known effector of G(q), but depends on a tetraspanin protein. Our work has identified an arrestin-independent endocytic pathway of G protein-coupled receptor in the fly. This pathway may also function in mammals and mediate an early feedback regulation of receptor signaling.

IntragenicCAMTA1rearrangements cause non-progressive congenital ataxia with or without intellectual disability

“…The Q-PCR control of the deletion finally defined that the CNV was purely intronic (S Scherer, personal communication). Apart from the identification of intragenic CAMTA1 deletions/duplication, other evidence supports the disease-causing role of the gene as: (i) the CAMTA1 gene appears to be predominantly expressed in the human brain17 and its integrity is necessary for visual response in the fruit fly, which suggests that it has a superior function in mammalians;22 23 29 (ii) the cellular functions of genes being under CAMTA1 transcriptional control suggest a putative role of CAMTA1 in promoting neuronal differentiation and are responsible for ID ± ASD when genes such as SHANK3, CHRNA7, NRG1 and 2, CAMK4 and CASK are mutated;30 31 and (iii) a replicated association between a CAMTA1 allele (rs4908449; p=0.0002) and differential performance in normal episodic memory, which adds CAMTA1 to the list of calcium-responsive proteins responsible for memory processes in humans 32 33…”

Dynamin- and Rab5-dependent endocytosis is required to preventDrosophilaphotoreceptor degeneration

“…In particular, a role for the heterotrimeric G-proteins and in particular Gqe (officially known as G49B) remains to be tested. The phenotype of a loss-of-function allele (the strong hypomorphic mutation Gqe 1 ) does not resemble the ninaE l17 phenotype (Han et al, 2007) (data not shown). However, this might be because Gqe 1 is not a null allele (Lee et al, 1990).…”

Phototransduction in Drosophila

“…Recently, people try to reveal the mechanisms of deactivation in visual response, because timely deactivation is required for the receiving of subsequent stimulation and preventing toxicity induced by excessive Ca 2+ influx [51].…”