Proper function of the drosophila trp gene product during pupal development is important for normal visual transduction in the adult

doi:10.1016/0896-6273(89)90117-7

Neuron

Volume 3, Issue 1, July 1989, Pages 81-94

https://doi.org/10.1016/0896-6273(89)90117-7 Get rights and content

Abstract

The response of invertebrate photoreceptors consists of the summation of quantum bumps, each representing the response to a single photon. The bumps adapt depending on the intensity of the stimulus: their average size is relatively large in dim light and small in bright light. The rate of occurrence of the bumps varies proportionally with light intensity. In the Drosophila mutant trp, unlike in the wild type, the rate does not increase with increasing light intensity and the bumps do not adapt. Here we report an analysis of the trp gene and its expression in normal and mutant flies. Our results suggest that the trp protein is a novel photoreceptor membrane-associated protein, that this protein is not required for the occurrence of bumps but is necessary for adaptation, and that proper function of the trp gene product during pupal development is important for normal visual transduction in the adult.

References (54)

K.M. Baer et al.
Light and GTP activated hydrolysis of phosphatidylinositol bisphosphate in squid photoreceptor membranes
J. Biol. Chem.
(1988)
W. Bender et al.
Chromosomal walking and jumping to isolate DNA from the Ace and rosy loci and the bithorax complex in Drosophila melanogaster
J. Mol. Biol.
(1983)
B.T. Bloomquist et al.
Isolation of a putative phospholipase C gene of Drosophila, norpA, and its role in phototransduction
Cell
(1988)
G. Brawerman
mRNA decay: finding the right targets
Cell
(1989)
D.J. Cosens et al.
The fine structure of the eye of a visual mutant A-type, of Drosophila melanogaster
J. Insect Physiol.
(1972)
J.R. Feramisco et al.
Optimal spatial requirements for the location of basic residues in peptide substrates for the cyclic AMP-dependent protein kinase
J. Biol. Chem.
(1980)
P.K. Ghosh et al.
Heterogeneity and 5′ terminal structures of the late RNAs of simian virus 40
J. Mol. Biol.
(1978)
S. Henikoff
Unidirectional digestion with exonuclease III in DNA sequence analysis
Meth. Enzymol.
(1987)
J. Kyte et al.
A simple model for displaying the hydropathic character of a protein
J. Mol. Biol.
(1982)
L.S. Levy et al.
The selection, expression, and organization of a set of head-specific genes in Drosophila
Dev. Biol.
(1982)

D.F. Ready et al.

Development of the Drosophila retina, a neurocrystalline lattice

Dev. Biol.

(1976)

R. Reinke et al.

Chaoptin, a cell surface glycoprotein required for Drosophila photoreceptor cell morphogenensis contains a repeat motif found in yeast and human

Cell

(1988)

H. Vogel et al.

Models for the structure of outer-membrane proteins of Escherichia coli derived from Raman spectroscopy and prediction methods

J. Mol. Biol.

(1986)

J. Bacigalupo et al.

Second messenger in invertebrate phototransduction

M.J. Berridge

Inositol phosphates as second messengers

M.J. Berridge

Inositol trisphosphate and diacylglycerol: two interacting second messengers

Annu. Rev. Biochem.

(1987)

K.-J. Chang et al.

Antibody specific to the alpha subunit of the guanine nucleotide-binding regulatory protein G: developmental appearance and immunocytochemical localization in brain

J.M. Chirgwin et al.

Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease

Biochemistry

(1979)

P.Y. Chou et al.

Prediction of protein conformation

Biochemistry

(1974)

P.Y. Chou et al.

Prediction of the secondary structure of proteins from their amino acid sequence

Adv. Enzymol.

(1978)

D.J. Cosens et al.

Abnormal electroretinogram from a Drosophila mutant

Nature

(1969)

L.G. Davis et al.

Basic Methods in Molecular Biology

(1986)

O. Devary et al.

Coupling of photoexcited rhodopsin to inositol phospholipid hydrolysis in fly photoreceptors

R.F. Doolittle

Of URF's and ORF's: a primer on how to analyze derived amino acid sequences

A. Fein et al.

Photoreceptor excitation and adaptation by inositol 1,4,5-, trisphosphate

Nature

(1984)

A.P. Feinberg et al.

Addendum to A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity

Anal. Biochem.

(1984)

M.C. Frisardi et al.

Position effect variegation of an acid phosphatase gene in Drosophila melanogaster

Mol. Gen. Genet.

(1984)

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Transient receptor potential canonical (TRPC) channels constitute a group of receptor-operated calcium-permeable nonselective cation channels of the TRP superfamily. The seven mammalian TRPC members, which can be further divided into four subgroups (TRPC1, TRPC2, TRPC4/5, and TRPC3/6/7) based on their amino acid sequences and functional similarities, contribute to a broad spectrum of cellular functions and physiological roles. Studies have revealed complexity of their regulation involving several components of the phospholipase C pathway, G_i and G_o proteins, and internal Ca²⁺ stores. Recent advances in cryogenic electron microscopy have provided several high-resolution structures of TRPC channels. Growing evidence demonstrates the involvement of TRPC channels in diseases, particularly the link between genetic mutations of TRPC6 and familial focal segmental glomerulosclerosis. Because TRPCs were discovered by the molecular identity first, their pharmacology had lagged behind. This is rapidly changing in recent years owning to great efforts from both academia and industry. A number of potent tool compounds from both synthetic and natural products that selective target different subtypes of TRPC channels have been discovered, including some preclinical drug candidates. This review will cover recent advancements in the understanding of TRPC channel regulation, structure, and discovery of novel TRPC small molecular probes over the past few years, with the goal of facilitating drug discovery for the study of TRPCs and therapeutic development.
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The first of the Transient Receptor Potential (TRP) ion channel was discovered in a mutant of the Drosophila melanogaster fly that was unable to respond to repeated or constant bright light stimulation (Cosens and Manning, 1969). The trp mutation was in a gene encoding an integral membrane protein with six trans-membrane domains (Wong et al., 1989). Electrophysiological analysis revealed that it was a calcium-permeable, non-selective cation channel that opens in response to signalling from activated rhodopsin (Hardie and Minke, 1992).
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^‡: Present address: Department of Ophthalmology, Duke University Medical Center, Box 3802 DUMC, Durham, North Carolina 27710.

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Neuron

ArticleProper function of the drosophila trp gene product during pupal development is important for normal visual transduction in the adult

Abstract

J. Biol. Chem.

J. Mol. Biol.

Cell

Cell

J. Insect Physiol.

J. Biol. Chem.

J. Mol. Biol.

Meth. Enzymol.

J. Mol. Biol.

Dev. Biol.

Dev. Biol.

Cell

J. Mol. Biol.

Second messenger in invertebrate phototransduction

Inositol phosphates as second messengers

Inositol trisphosphate and diacylglycerol: two interacting second messengers

Annu. Rev. Biochem.

Antibody specific to the alpha subunit of the guanine nucleotide-binding regulatory protein G: developmental appearance and immunocytochemical localization in brain

Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease

Biochemistry

Prediction of protein conformation

Biochemistry

Prediction of the secondary structure of proteins from their amino acid sequence

Adv. Enzymol.

Abnormal electroretinogram from a Drosophila mutant

Nature

Basic Methods in Molecular Biology

Coupling of photoexcited rhodopsin to inositol phospholipid hydrolysis in fly photoreceptors

Of URF's and ORF's: a primer on how to analyze derived amino acid sequences

Photoreceptor excitation and adaptation by inositol 1,4,5-, trisphosphate

Nature

Addendum to A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity

Anal. Biochem.

Position effect variegation of an acid phosphatase gene in Drosophila melanogaster

Mol. Gen. Genet.

Article
Proper function of the drosophila trp gene product during pupal development is important for normal visual transduction in the adult