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Liprin-alpha is required for photoreceptor target selection in Drosophila.

ABSTRACT: Classical cadherin-mediated interactions between axons and dendrites are critical to target selection and synapse assembly. However, the molecular mechanisms by which these interactions are controlled are incompletely understood. In the Drosophila visual system, N-cadherin is required in both photoreceptor (R cell) axons and their targets to mediate stabilizing interactions required for R cell target selection. Here we identify the scaffolding protein Liprin-alpha as a critical component in this process. We isolated mutations in Liprin-alpha in a genetic screen for mutations affecting the pattern of synaptic connections made by R1-R6 photoreceptors. Using eye-specific mosaics, we demonstrate a previously undescribed, axonal function for Liprin-alpha in target selection: Liprin-alpha is required to be cell-autonomous in all subtypes of R1-R6 cells for their axons to reach their targets. Because Liprin-alpha, the receptor tyrosine phosphatase LAR, and N-cadherin share qualitatively similar mutant phenotypes in R1-R6 cells and are coexpressed in R cells and their synaptic targets, we infer that these three genes act at the same step in the targeting process. However, unlike N-cadherin, neither Liprin-alpha nor LAR is required postsynaptically for R cells to project to their correct targets. Thus, these two proteins, unlike N-cadherin, are functionally asymmetric between axons and dendrites. We propose that the adhesive mechanisms that link pre- and postsynaptic cells before synapse formation may be differentially regulated in these two compartments.

SUBMITTER: Choe KM

PROVIDER: S-EPMC1544216 | biostudies-other | 2006 Aug

REPOSITORIES: biostudies-other

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Liprin-alpha is required for photoreceptor target selection in Drosophila.

Choe Kwang-Min KM Prakash Saurabh S Bright Ali A Clandinin Thomas R TR

Proceedings of the National Academy of Sciences of the United States of America 20060724 31

Classical cadherin-mediated interactions between axons and dendrites are critical to target selection and synapse assembly. However, the molecular mechanisms by which these interactions are controlled are incompletely understood. In the Drosophila visual system, N-cadherin is required in both photoreceptor (R cell) axons and their targets to mediate stabilizing interactions required for R cell target selection. Here we identify the scaffolding protein Liprin-alpha as a critical component in this ...[more]

PMID: 16864799

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Project description:Rhodopsins are light-detecting proteins coupled with retinal chromophores essential for visual function. Coincidentally, dysfunctional Rhodopsin homeostasis underlies retinal degeneration in humans and model organisms. Drosophila ninaEG69D mutant is one such example, where the encoded Rh1 protein imposes endoplasmic reticulum (ER) stress and causes light-dependent retinal degeneration. The underlying reason for such light-dependency remains unknown. Here, we report that Drosophila fatty acid binding protein (fabp) is a gene induced in ninaEG69D/+ photoreceptors, and regulates light-dependent Rhodopsin-1 (Rh1) protein clearance and photoreceptor survival. Specifically, our photoreceptor-specific gene expression profiling study in ninaEG69D/+ flies revealed increased expression of fabp together with other genes that control light-dependent Rh1 protein degradation. fabp induction in ninaEG69D photoreceptors required vitamin A and its transporter genes. In flies reared under light, loss of fabp caused an accumulation of Rh1 proteins in cytoplasmic vesicles. The increase in Rh1 levels under these conditions was dependent on Arrestin2 that mediates feedback inhibition of light-activated Rh1. fabp mutants exhibited light-dependent retinal degeneration, a phenotype also found in other mutants that block light-induced Rh1 degradation. These observations reveal a previously unrecognized link between light-dependent Rh1 proteostasis and the ER-stress imposing ninaEG69D mutant that cause retinal degeneration. Author summary Rhodopsins are light-detecting proteins that use retinoids as chromophore co-factors. Rhodopsins are tighly regulated in photoreceptors, as dysfunctional Rhodopsins cause photoreceptor degeneration. The precise mechanisms by which photoreceptors regulate Rhodopsin homeostasis remains unclear. Here, we report that Drosophila fatty acid binding protein (fabp) is a gene required for Rhodopsin-1 (Rh1) protein homeostasis and photoreceptor survival. Specifically, we found that fabp is among the genes induced by an endoplasmic reticulum (ER) stress-imposing Rhodopsin-1 (Rh1) mutant, ninaEG69D, which serves as a Drosophila model for Retinitis Pigmentosa. We further found that fabp induction in ninaEG69D photoreceptors required vitamin A and its transporter genes. fabp was required in photoreceptors to help degrade light-activated Rh1. In the absence of fabp, Rh1 accumulated in cytoplasmic vesicles in a light-dependent manner, and exhibited light-dependent retinal degeneration. These observations indicate that fabp is required for light-induced Rh1 degradation and photoreceptor survival.

Dataset Information

Liprin-alpha is required for photoreceptor target selection in Drosophila.

Publications

Liprin-alpha is required for photoreceptor target selection in Drosophila.

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