Trp channels
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Transcript of Trp channels
Understanding of sensory physiology.
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
Structural differences between TRP channels
Annu. Rev. Biochem. 2007. 76:387–417
The trp phenotype.
Physiol Rev • VOL 82 • APRIL 2002 • www.prv.org
…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.
Some TRP channels are regulated by inositol phosphates or by phosphoinositides
The EMBO Journal (2008) 27, 2809–2816
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
It turns out that a TRP-Like protein (TRPL)
J. Neurosci., September 15, 2000, 20(18):6797–6803
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
The first mammalian TRPs
Proc. Natl. Acad. Sci. USA 92 (1995)
“That TRP is conserved from nematodes to humans,”
Biochem. J. (1995) 311, 41-44
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.
A tremendously important finding in the TRP field was the discovery of the capsaicin receptor (TRPV1)
NATURE | VOL 389 | 23 OCTOBER 1997
Thermo TRP channels.
The Thermo-TRP channels.
Current Opinion in Neurobiology 2007, 17:490–497
TRP Channels And Thermosensitivity
Am J Physiol Regul Integr Comp Physiol 292:R64-R76, 2007.
TRP channels in hot and cold sensation.
Trends in Neurosciences Vol.31 No.6
The mechanism of direct activation of thermoTRPs.
NATURE |VOL 430 | 12 AUGUST 2004 | pp. 748-754
Cooling activates TRPM8 by shifting the voltage dependence of activation.
NATURE |VOL 430 | 12 AUGUST 2004 | pp. 748-754
Heating activates TRPV1 by shifting the voltage dependence of activation.
NATURE |VOL 430 | 12 AUGUST 2004 | pp. 748-754
A two-state model accurately predicts the temperature-dependent behaviour
of TRPM8 and TRPV1.
NATURE |VOL 430 | 12 AUGUST 2004 | pp. 748-754
Requirement for TRPA1 for sensing comfortably cool temperatures in
Drosophila.
NATURE NEUROSCIENCE VOLUME 11 NUMBER 8 AUGUST 2008 pp. 871-873.
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.
Two modes for thermal activation of TRP channels.
Eur J Physiol (2011) 461:499–506
Gq/NORPA/TRP signaling cascade is also used in Drosophila for
sensing odorants
Current Biology 20, 1672–1678, September 28, 2010
Detecting a small subset of tastants
| PNAS | May 4, 2010 | vol. 107 | no. 18 pp. 8440–8445
TRP channel (TRPM5) functions in the response to all bitter and
sweet tastants
Cel
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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
painless, a Drosophila Gene Essential for Nociception
Cel
l 200
3 11
3:26
1–27
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A Drosophila Mechanosensory Transduction Channel
SCIENCE VOL 287 24 MARCH 2000 pp. 2229-2234
Two interdependent TRPV channel subunits, Inactive and Nanchung,
mediate hearing in Drosophila.
A TRPV family ion channel required for hearing in Drosophila.
NATURE | VOL 424 | 3 JULY 2003 | pp. 81-84
Mechanotransduction in vertebrate hair cells.
Nat Rev Neurosci 2008. no. 8: pp. 510–521
TRPN channel (NOMPC) is activated by mechanical stimulation on a
microsecond time scale (~650 μs)
Neuron 67, 381–391, August 12, 2010
TRP channels and diseases.
Eur J Physiol (2011) 461:499–506Eur J Physiol (2010) 460:437–450
The neurodegeneration resulted from impaired clearance of early
apoptotic neurons
Cell 135, 838–851, November 28, 2008
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.