The trp gene is essential for a light-activated Ca2+ channel in Drosophila photoreceptors

doi:10.1016/0896-6273(92)90086-S

Neuron

Volume 8, Issue 4, April 1992, Pages 643-651

https://doi.org/10.1016/0896-6273(92)90086-S Get rights and content

Abstract

Invertebrate phototransduction is an important model system for studying the ubiquitous inositol-lipid signaling system. In the transient receptor potential (trp) mutant, one of the most intensively studied transduction mutants of Drosophila, the light response quickly declines to baseline during prolonged intense light. Using whole-cell recordings from Drosophila photoreceptors, we show that the wild-type response is mediated by at least two functionally distinct classes of light-sensitive channels and that both the trp mutation and a Ca²⁺ channel blocker (La³⁺) selectively abolish one class of channel with high Ca²⁺ permeability. Evidence is also presented that Ca²⁺ is necessary for excitation and that Ca²⁺ depletion mimics the trp phenotype. We conclude that the recently sequenced trp protein represents a class of light-sensitive channel required for inositide-mediated Ca²⁺ entry and suggest that this process is necessary for maintained excitation during intense illumination in fly photoreceptors.

References (58)

M.J. Berridge
Calcium oscillations
J. Biol. Chem.
(1990)
B.T. Bloomquist et al.
Isolation of a putative phospholipase C gene of Drosophila, norpA, and its role in phototransduction
Cell
(1988)
H.M. Brown et al.
Intracellular calcium changes in Balanus photoreceptors, a study with calcium ion-selective electrodes and Arsenazo III
Cell Calcium
(1988)
J.J. Feng et al.
Excitation of Limulus photoreceptors by hydrolysis-resistant analogs of cGMP and cAMP
Brain Res.
(1991)
R.C. Hardie et al.
Novel potassium channels encoded by the Shaker locus in Drosophila photoreceptors
Neuron
(1991)
R.F. Irvine
“Quantal” Ca²⁺ release and the control of Ca²⁺ entry by inositol phosphates—a possible mechanism
FEBS Lett.
(1990)
B. Minke et al.
Light induced sodium dependent accumulation of calcium and potassium in the extracellular space of the bee retina
Vision Res.
(1986)
C. Montell et al.
Molecular characterization of the Drosophila trp locus: a putative integral membrane protein required for phototransduction
Neuron
(1989)
R. Ranganathan et al.
The molecular genetics of invertebrate phototransduction
Trends Neurosci.
(1991)
H. Takemura et al.
Activation of calcium entry by the tumor promoter, thapsigargin, in parotid acinar cells. Evidence that an intracellular pool, and not an inositol phosphate, regulates calcium fluxes at the plasma membrane
J. Biol. Chem.
(1989)

B. Walz

Calcium-sequestering smooth endoplasmic reticulum in retinula cells of the blowfly

J. Ultrastruct. Res.

(1982)

F. Wong et al.

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

Neuron

(1989)

O. Baumann et al.

Electron probe microanalysis of calcium release and magnesium uptake by endoplasmic reticulum in bee photoreceptors

G.S.J. Bird et al.

Activation of Ca²⁺ entry into acinar cells by a non-phosphorylatable inositol trisphosphate

Nature

(1991)

B.A. Block et al.

Structural evidence for direct interaction between the molecular components of the transverse tubule/sarcoplasmic reticulum junction in skeletal muscle

J. Cell Biol.

(1988)

S.R. Bolsover et al.

Calcium an intracellular messenger of light adaptation also participates in excitation of Limulus ventral photoreceptors

J. Physiol. (Lond.)

(1985)

J.E. Brown et al.

Changes in intracellular free calcium during illumination of invertebrate photoreceptors: detection with Aequorin

J. Gen. Physiol.

(1974)

J.E. Brown et al.

Myo-inositol polyphosphate maybe a messenger for visual excitation in Limulus photoreceptors

Nature

(1984)

D.J. Cosens et al.

Abnormal electroretinogram from a Drosophila mutant

Nature

(1969)

A. Deckert et al.

Electrogenic Na+-Ca2+ exchanger, the link between intra- and extracellular calcium in the Limulus ventral photoreceptor

J. Physiol.

(1991)

O.O. Devary et al.

Coupling of photoexcited rhodopsin to inositol phospholipid hydrolysis in fly photoreceptors

A. Fein et al.

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

Nature

(1984)

T.M. Frank et al.

The role of the inositol phosphate cascade in visual excitation of invertebrate microvillar photoreceptors

J. Gen. Physiol.

(1991)

T. Furichi et al.

Primary structure and functional expression of the inositol 1,4,5-trisphosphate-binding protein P₄₀₀

Nature

(1989)

R.C. Hardie

Functional organization of the fly retina

Prog. Sens. Physiol.

(1985)

R.C. Hardie

Whole-cell recordings of the light induced current in dissociated Drosophila photoreceptors, evidence for feedback by calcium permeating the light-sensitive channels

R.C. Hardie

Voltage-sensitive potassium channels in Drosophila photoreceptors

J. Neurosci.

(1991)

B. Hille

Ionic Channels of Excitable Membranes

(1984)

P. Hochstrate

Lanthanum mimicks the trp photoreceptor mutant of Drosophila in the blowfly Calliphora

J. Comp. Physiol. (A)

(1989)

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Neuron

ArticleThe trp gene is essential for a light-activated Ca2+ channel in Drosophila photoreceptors

Abstract

J. Biol. Chem.

Cell

Cell Calcium

Brain Res.

Neuron

FEBS Lett.

Vision Res.

Neuron

Trends Neurosci.

J. Biol. Chem.

J. Ultrastruct. Res.

Neuron

Electron probe microanalysis of calcium release and magnesium uptake by endoplasmic reticulum in bee photoreceptors

Activation of Ca2+ entry into acinar cells by a non-phosphorylatable inositol trisphosphate

Nature

Structural evidence for direct interaction between the molecular components of the transverse tubule/sarcoplasmic reticulum junction in skeletal muscle

J. Cell Biol.

Calcium an intracellular messenger of light adaptation also participates in excitation of Limulus ventral photoreceptors

J. Physiol. (Lond.)

Changes in intracellular free calcium during illumination of invertebrate photoreceptors: detection with Aequorin

J. Gen. Physiol.

Myo-inositol polyphosphate maybe a messenger for visual excitation in Limulus photoreceptors

Nature

Abnormal electroretinogram from a Drosophila mutant

Nature

Electrogenic Na+-Ca2+ exchanger, the link between intra- and extracellular calcium in the Limulus ventral photoreceptor

J. Physiol.

Coupling of photoexcited rhodopsin to inositol phospholipid hydrolysis in fly photoreceptors

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

Nature

The role of the inositol phosphate cascade in visual excitation of invertebrate microvillar photoreceptors

J. Gen. Physiol.

Primary structure and functional expression of the inositol 1,4,5-trisphosphate-binding protein P400

Nature

Functional organization of the fly retina

Prog. Sens. Physiol.

Whole-cell recordings of the light induced current in dissociated Drosophila photoreceptors, evidence for feedback by calcium permeating the light-sensitive channels

Voltage-sensitive potassium channels in Drosophila photoreceptors

J. Neurosci.

Ionic Channels of Excitable Membranes

Lanthanum mimicks the trp photoreceptor mutant of Drosophila in the blowfly Calliphora

J. Comp. Physiol. (A)

Article
The trp gene is essential for a light-activated Ca²⁺ channel in Drosophila photoreceptors

Activation of Ca²⁺ entry into acinar cells by a non-phosphorylatable inositol trisphosphate

Primary structure and functional expression of the inositol 1,4,5-trisphosphate-binding protein P₄₀₀