A new genetic model for calcium induced autophagy and ER-stress in Drosophila photoreceptor cells

The light response in Drosophila photoreceptor cells is mediated by a series of proteins that assemble into a macromolecular complex referred to as the signalplex. The central player in the signalplex is inactivation no afterpotential D (INAD), a protein consisting of a tandem array of five PDZ domains. At least seven proteins bind INAD, including the transient receptor potential (TRP) channel, which depends on INAD for localization to the phototransducing organelle, the rhabdomere. However, the determinants required for localization of INAD are not known. In this work, we showed that INAD was required for retention rather than targeting of TRP to the rhabdomeres. In addition, we demonstrated that TRP bound to INAD through the COOH terminus, and this interaction was required for localization of INAD. Other proteins that depend on INAD for localization, phospholipase C and protein kinase C, also mislocalized. However, elimination of any other member of the signalplex had no impact on the spatial distribution of INAD. A direct interaction between TRP and INAD did not appear to have a role in the photoresponse independent of localization of multiple signaling components. Rather, the primary function of the TRP/ INAD complex is to form the core unit required for localization of the signalplex to the rhabdomeres.

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A role for the extracellular domain of Crumbs in morphogenesis of Drosophila photoreceptor cells

European Journal of Cell Biology ◽

10.1016/j.ejcb.2009.07.006 ◽

2009 ◽

Vol 88 (12) ◽

pp. 765-777 ◽

Cited By ~ 25

Author(s):

Mélisande Richard ◽

Nadine Muschalik ◽

Ferdi Grawe ◽

Susann Özüyaman ◽

Elisabeth Knust

Keyword(s):

Photoreceptor Cells ◽

Extracellular Domain ◽

Drosophila Photoreceptor

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Identification of genes required for apical protein trafficking in Drosophila photoreceptor cells

10.1101/653469 ◽

2019 ◽

Author(s):

Azadeh Laffafian ◽

Ulrich Tepass

Keyword(s):

Protein Trafficking ◽

Apical Membrane ◽

Vesicle Trafficking ◽

Retinal Disease ◽

Photoreceptor Cells ◽

Fruit Fly ◽

Light Sensing ◽

Human Orthologs ◽

Apical Trafficking ◽

Drosophila Photoreceptor

AbstractDrosophila photoreceptor cells (PRCs) are highly polarized epithelial cells. Their apical membrane is further subdivided into the stalk membrane and the light-sensing rhabdomere. The photo-pigment Rhodopsin1 (Rh1) localizes to the rhabdomere, whereas the apical determinant Crumbs (Crb) is enriched at the stalk membrane. The proteoglycan Eyes shut (Eys) is secreted through the apical membrane into an inter-rhabdomeral space. Rh1, Crb, and Eys are essential for PRC development, normal vision, and PRC survival. Human orthologs of all three proteins have been linked to retinal degenerative diseases. Here, we describe an RNAi-based screen examining the importance of approximately 240 trafficking-related genes in apical trafficking of Eys, Rh1, and Crb. We found 28 genes that have an effect on the localization and/or levels of these apical proteins and analyzed several factors in more detail. We show that the Arf GEF protein Sec71 is required for biosynthetic traffic of both apical and basolateral proteins, that the exocyst complex and the microtubule-based motor proteins dynein and kinesin promote the secretion of Eys and Rh1, and that Syntaxin 7/Avalanche controls the endocytosis of Rh1, Eys, and Crb.Article summeryPhotoreceptor cells (PRCs) rely on polarized vesicle trafficking to deliver key secreted and transmembrane proteins to their correct locations. Failure to do so causes defects in PRC development, function, and survival leading to retinal disease. Using the fruit fly Drosophila as a model we have identified 28 genes that are required for the trafficking of the three apical proteins Rhodopsin 1, Crumbs, and Eyes Shut. Human homologs of all three genes are associated with retinal degeneration. We characterized several genes to reveal novel mechanisms of vesicle trafficking in photoreceptor cells at different points in the biosynthetic or endocytotic pathways.

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Mechanism and role of PDZ domains in signaling complex assembly

Journal of Cell Science ◽

10.1242/jcs.114.18.3219 ◽

2001 ◽

Vol 114 (18) ◽

pp. 3219-3231 ◽

Cited By ~ 20

Author(s):

Baruch Z. Harris ◽

Wendell A. Lim

Keyword(s):

Cell Signaling ◽

Pdz Domain ◽

Photoreceptor Cells ◽

Protein Recognition ◽

Pdz Domains ◽

Peptide Motifs ◽

Signaling Complex ◽

Multicellular Organisms ◽

Drosophila Photoreceptor

PDZ domains are protein-protein recognition modules that play a central role in organizing diverse cell signaling assemblies. These domains specifically recognize short C-terminal peptide motifs, but can also recognize internal sequences that structurally mimic a terminus. PDZ domains can therefore be used in combination to bind an array of target proteins or to oligomerize into branched networks. Several PDZ-domain-containing proteins play an important role in the transport, localization and assembly of supramolecular signaling complexes. Examples of such PDZ-mediated assemblies exist in Drosophila photoreceptor cells and at mammalian synapses. The predominance of PDZ domains in metazoans indicates that this highly specialized scaffolding module probably evolved in response to the increased signaling needs of multicellular organisms.

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Odor suppression of voltage-gated currents contributes to the odor-induced response in olfactory neurons

AJP Cell Physiology ◽

10.1152/ajpcell.1999.277.6.c1086 ◽

1999 ◽

Vol 277 (6) ◽

pp. C1086-C1099 ◽

Cited By ~ 9

Author(s):

Magdalena Sanhueza ◽

Juan Bacigalupo

Keyword(s):

Time Dependence ◽

Physiological Role ◽

Photoreceptor Cells ◽

Signaling Cascade ◽

Induced Response ◽

Olfactory Neurons ◽

Voltage Gated ◽

A Current ◽

Drosophila Photoreceptor ◽

Ion Conductances

Olfactory chemotransduction involves a signaling cascade. In addition to triggering transduction, odors suppress ion conductances. By stimulating with brief odorant pulses, we observed a current associated with odor-induced suppression of voltage-gated conductances and studied its time dependence. We characterized this suppression current in isolated Caudiverbera caudiverberaolfactory neurons. All four voltage-gated currents are suppressed by odor pulses in almost every neuron, and suppression is caused by odors inducing excitation and by those inducing inhibition, indicating a nonselective phenomenon, in contrast to transduction. Suppression has a 10-fold shorter latency than transduction. Suppression was more pronounced when odors were applied to the soma than to the cilia, opposite to transduction. Suppression was also present in rat olfactory neurons. Furthermore, we could induce it in Drosophila photoreceptor cells, demonstrating its independence from the chemotransduction cascade. We show that odor concentrations causing suppression are similar to those triggering chemotransduction and that both suppression and transduction contribute to the odor response in isolated olfactory neurons. Furthermore, suppression affects spiking, implying a possible physiological role in olfaction.

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Ca2+ Signaling in Drosophila Photoreceptor Cells

Advances in Experimental Medicine and Biology - Calcium Signaling ◽

10.1007/978-3-030-12457-1_34 ◽

2019 ◽

pp. 857-879

Author(s):

Olaf Voolstra ◽

Armin Huber

Keyword(s):

Photoreceptor Cells ◽

Drosophila Photoreceptor

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Drosophila Photoreceptor Cells Exploited for the Production of Eukaryotic Membrane Proteins: Receptors, Transporters and Channels

PLoS ONE ◽

10.1371/journal.pone.0018478 ◽

2011 ◽

Vol 6 (4) ◽

pp. e18478 ◽

Cited By ~ 8

Author(s):

Valérie Panneels ◽

Ines Kock ◽

Jacomine Krijnse-Locker ◽

Meriem Rezgaoui ◽

Irmgard Sinning

Keyword(s):

Membrane Proteins ◽

Photoreceptor Cells ◽

Eukaryotic Membrane Proteins ◽

Drosophila Photoreceptor

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A novel homozygous missense mutation p.P388S in TULP1 causes protein instability and retinitis pigmentosa

10.1101/2020.12.04.20238931 ◽

2020 ◽

Author(s):

DaNae R. Woodard ◽

Chao Xing ◽

Pratyusha Ganne ◽

Hanquan Liang ◽

Avinash Mahindrakar ◽

...

Keyword(s):

Retinitis Pigmentosa ◽

Er Stress ◽

Subcellular Distribution ◽

Protein Function ◽

Cultured Cells ◽

Retinal Pigment ◽

Photoreceptor Cells ◽

Causative Mutation ◽

The Individual ◽

Systemic Examination

ABSTRACTPurposeRetinitis pigmentosa (RP) is an inherited retinal disorder that results in the degeneration of photoreceptor cells, ultimately leading to severe visual impairment. We characterized a consanguineous family from Southern India wherein an individual in his 20’s presented with night blindness since childhood. The purpose of this study was to identify the causative mutation for RP in this individual as well as characterize how the mutation may ultimately affect protein function.MethodsWe performed a complete ophthalmologic examination of the proband followed by exome sequencing. The identified mutation was then modeled in cultured cells, evaluating its expression, solubility (both by western blot), subcellular distribution (confocal microscopy), and testing whether this variant induced endoplasmic reticulum (ER) stress (qPCR and western blotting).ResultsThe proband presented with generalized and parafoveal retinal pigment epithelial atrophy with bone spicule pigmentation in the mid periphery and arteriolar attenuation. Optical coherence tomography scans through the macula of both eyes showed atrophy of outer retinal layers with loss of the ellipsoid zone, whereas systemic examination of this individual was normal. The proband’s parents and sibling were asymptomatic and had normal funduscopic examinations. We discovered a novel homozygous p.Pro388Ser mutation in the tubby-like protein 1 (TULP1) gene in the individual with RP. In cultured cells, the P388S mutation does not alter the subcellular distribution of TULP1 or induce ER stress when compared to wild-type TULP1, but instead significantly lowers protein stability as indicated by steady-state and cycloheximide-chase experiments.ConclusionsThese results add to the list of known TULP1 mutations associated with RP and suggest a unique pathogenic mechanism in TULP1-induced RP, which may be shared amongst select mutations in TULP1.

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