trp channels

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Understanding of sensory physiology.

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Page 1: Trp channels

Understanding of sensory physiology.

Page 2: Trp channels

The family of T(ransient) R(eceptor) P(otential) ion channels

J Cell Sci November 15, 2004  117, 5707-5709

Annu. Rev. Biochem. 2007. 76:387–417

Page 3: Trp channels

Structural differences between TRP channels

Annu. Rev. Biochem. 2007. 76:387–417

Page 4: Trp channels

The trp phenotype.

Physiol Rev • VOL 82 • APRIL 2002 • www.prv.org

Page 5: Trp channels

…but we still considered the possibility that TRP was a channel or transporter.

(1) The prior indirect evidence from other laboratories thatintracellular

Ca2+ levels were decreased in the trp mutant.

(2) That TRP was situated in the plasma membrane.

(3) Was structurally related to known channels and transporters; and

(4) Raised the possibility that TRP might be a channel that promotes

Ca2+ entry.

Page 6: Trp channels

Some TRP channels are regulated by inositol phosphates or by phosphoinositides

The EMBO Journal (2008) 27, 2809–2816

Page 7: Trp channels

The TRP protein in Drosophila: an Ion Channel?

They don’t has conclusive evidence that TRP was a channel, however. A second

key observationwas a patch-clamp analysis by Roger Hardie and Baruch Minke

that demonstrated that light-dependent Ca2+ influx was reduced significantly in

the trp mutant.

The whole-cell recording analysis demonstrated that a moderately Ca2+ selective

influx pathway was eliminated in the trp mutant

Page 8: Trp channels

It turns out that a TRP-Like protein (TRPL)

J. Neurosci., September 15, 2000, 20(18):6797–6803

Page 9: Trp channels

The direct evidence that Drosophila TRP comprises a subunit of a Ca2+ permeable channel in vivo

The results of the analyses demonstrated that this mutation dramatically reduced Ca2+ selectivity in Drosophila photo receptor cells.

J. Neurosci., January 17, 2007 • 27(3):604 –615

Page 10: Trp channels

The first mammalian TRPs

Proc. Natl. Acad. Sci. USA 92 (1995)

Page 11: Trp channels

“That TRP is conserved from nematodes to humans,”

Biochem. J. (1995) 311, 41-44

Page 12: Trp channels

Ion Ion channelchannel

A New function A New function ReferencesReferences

TRPC2,

TRPC7,

TRPP1

The first examples of ion channels fused to

enzyme domains.

• NATURE | VOL 411 | 31 MAY 2001 pp. 590-

595.

• NATURE | VOL 411 | 31 MAY 2001 pp. 595-

599.

• SCIENCE VOL 291 9 FEBRUARY 2001, pp.

1043-1047.

• SCIENCE VOL 293 17 AUGUST 2001, pp.

1327-1330.

TRPM6,

TRPM7.

A “chanzyme” related shown to underlie a

hypomagnesemia and hypocalcemia

NATURE GENETICS VOLUME 31 JUNE 2002,

PP. 166-170.

NATURE GENETICS VOLUME 31 JUNE 2002,

PP. 171-174.

TRPC3 Reported an in vivo conductance in the

mammalian brain resulting from activation

of a TRP channel.

NEURON, VOL. 24, SEPTEMBER, 1999, pp.

261–273.

TRPC1,

TRPC3

Activation by neurotrophins functioned in

growth cone guidance

NATURE | VOL 434 | 14 APRIL 2005 , pp. 894-

898.

NATURE | VOL 434 | 14 APRIL 2005 , pp. 898-

904.

Page 13: Trp channels

A tremendously important finding in the TRP field was the discovery of the capsaicin receptor (TRPV1)

NATURE | VOL 389 | 23 OCTOBER 1997

Page 14: Trp channels

Thermo TRP channels.

Page 15: Trp channels

The Thermo-TRP channels.

Current Opinion in Neurobiology 2007, 17:490–497

Page 16: Trp channels

TRP Channels And Thermosensitivity

Am J Physiol Regul Integr Comp Physiol 292:R64-R76, 2007.

Page 17: Trp channels

TRP channels in hot and cold sensation.

Trends in Neurosciences Vol.31 No.6

Page 18: Trp channels

The mechanism of direct activation of thermoTRPs.

NATURE |VOL 430 | 12 AUGUST 2004 | pp. 748-754

Page 19: Trp channels

Cooling activates TRPM8 by shifting the voltage dependence of activation.

NATURE |VOL 430 | 12 AUGUST 2004 | pp. 748-754

Page 20: Trp channels

Heating activates TRPV1 by shifting the voltage dependence of activation.

NATURE |VOL 430 | 12 AUGUST 2004 | pp. 748-754

Page 21: Trp channels

A two-state model accurately predicts the temperature-dependent behaviour

of TRPM8 and TRPV1.

NATURE |VOL 430 | 12 AUGUST 2004 | pp. 748-754

Page 22: Trp channels

Requirement for TRPA1 for sensing comfortably cool temperatures in

Drosophila.

NATURE NEUROSCIENCE VOLUME 11 NUMBER 8 AUGUST 2008 pp. 871-873.

Page 23: Trp channels

Requirement for phosphoinositide signaling cascade for

discriminating comfortably cool temperatures (18 versus 24 1C).

NATURE NEUROSCIENCE VOLUME 11 NUMBER 8 AUGUST 2008 pp. 871-873.

Page 24: Trp channels

Two modes for thermal activation of TRP channels.

Eur J Physiol (2011) 461:499–506

Page 25: Trp channels

Gq/NORPA/TRP signaling cascade is also used in Drosophila for

sensing odorants

Current Biology 20, 1672–1678, September 28, 2010

Page 26: Trp channels

Detecting a small subset of tastants

| PNAS | May 4, 2010 | vol. 107 | no. 18 pp. 8440–8445

Page 27: Trp channels

TRP channel (TRPM5) functions in the response to all bitter and

sweet tastants

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Page 28: Trp channels

OSM-9, A Novel Protein, Is Required for Olfaction, Mechanosensation, and Olfactory

Adaptation in Caenorhabditis elegans

The Journal of Neuroscience, November 1, 1997, 17(21):8259–8269

Page 29: Trp channels

painless, a Drosophila Gene Essential for Nociception

Cel

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Page 30: Trp channels

A Drosophila Mechanosensory Transduction Channel

SCIENCE VOL 287 24 MARCH 2000 pp. 2229-2234

Page 31: Trp channels

Two interdependent TRPV channel subunits, Inactive and Nanchung,

mediate hearing in Drosophila.

Page 32: Trp channels

A TRPV family ion channel required for hearing in Drosophila.

NATURE | VOL 424 | 3 JULY 2003 | pp. 81-84

Page 33: Trp channels

Mechanotransduction in vertebrate hair cells.

Nat Rev Neurosci 2008. no. 8: pp. 510–521

Page 34: Trp channels

TRPN channel (NOMPC) is activated by mechanical stimulation on a

microsecond time scale (~650 μs)

Neuron 67, 381–391, August 12, 2010

Page 35: Trp channels

TRP channels and diseases.

Eur J Physiol (2011) 461:499–506Eur J Physiol (2010) 460:437–450

Page 36: Trp channels

The neurodegeneration resulted from impaired clearance of early

apoptotic neurons

Cell 135, 838–851, November 28, 2008

Page 37: Trp channels

Concluding remarks Drosophila trp mutant remained obscure during 20 years. In wich time there was no especific predicition of a function for the trp

gene product Then this changed with amino acid sequence analys, wich showed the trp

gene product is a ion channel. The whole cell recording demostrated a reduction in a light dependent Ca+

+ influx in trp mutant cells. The analysis of a TRP isoform with mutation in the ion selectivity filter

solidified the concept that TRP was a Ca++ permeable channel. The TRP proteins they finded in humans in 1995. The TRP are golblar sensors of sensory input. The TRP human subfamilies are underlie disease. The TRP channels are sensory detectors in insect vectors.