The document summarizes research on TRP (Transient Receptor Potential) ion channels. Key findings include: (1) TRP channels were initially identified in Drosophila and their function was unclear for 20 years, (2) Amino acid sequencing revealed TRP's structural similarity to ion channels, (3) Electrophysiology experiments showed reduced calcium influx in TRP mutants, confirming TRP is a calcium-permeable channel, (4) TRP channels function as global sensors across species, detecting sensory stimuli like temperature, taste, smell, and mechanosensation, and (5) Malfunctions in human TRP channels can underlie diseases.

1. Understanding of sensory physiology.

2. 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

3. Structural differences between TRP
channels
Annu. Rev. Biochem. 2007. 76:387–417

4. The trp phenotype.
Physiol Rev • VOL 82 • APRIL 2002 • www.prv.org

5. …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.

6. Some TRP channels are regulated by
inositol phosphates or by
phosphoinositides
The EMBO Journal (2008) 27, 2809–2816

7. 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

8. It turns out that a TRP-Like protein
(TRPL)
J. Neurosci., September 15, 2000,
20(18):6797–6803

9. 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

10. The first mammalian TRPs
Proc. Natl. Acad. Sci. USA 92 (1995)

11. “That TRP is conserved from nematodes
to humans,”
Biochem. J. (1995) 311, 41-44

12. IonIon
channelchannel
A New functionA 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.

13. A tremendously important finding in the TRP
field was the discovery of the capsaicin
receptor (TRPV1)
NATURE | VOL 389 | 23 OCTOBER 1997

14. Thermo TRP channels.

15. The Thermo-TRP
channels.
Current Opinion in Neurobiology 2007, 17:490–497

16. TRP Channels And Thermosensitivity
Am J Physiol Regul Integr Comp Physiol
292:R64-R76, 2007.

17. TRP channels in
hot and cold
sensation.
Trends in Neurosciences Vol.31 No.6

18. The mechanism of direct activation
of thermoTRPs.
NATURE |VOL 430 | 12 AUGUST 2004 | pp. 748-754

19. Cooling activates TRPM8 by shifting
the voltage dependence of
activation.
NATURE |VOL 430 | 12 AUGUST 2004 | pp. 748-754

20. Heating activates TRPV1 by shifting the
voltage dependence of activation.
NATURE |VOL 430 | 12 AUGUST 2004 | pp. 748-754

21. A two-state model accurately predicts the
temperature-dependent behaviour of
TRPM8 and TRPV1.
NATURE |VOL 430 | 12 AUGUST 2004 | pp. 748-754

22. Requirement for TRPA1 for sensing
comfortably cool temperatures in
Drosophila.
NATURE NEUROSCIENCE VOLUME 11 NUMBER 8
AUGUST 2008 pp. 871-873.

23. 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.

24. Two modes for thermal activation of
TRP channels.
Eur J Physiol (2011) 461:499–506

25. Gq/NORPA/TRP signaling cascade is
also used in Drosophila for sensing
odorants
Current Biology 20, 1672–1678,
September 28, 2010

26. Detecting a small subset of
tastants
| PNAS | May 4, 2010 | vol. 107
| no. 18 pp. 8440–8445

27. TRP channel (TRPM5) functions in
the response to all bitter and sweet
tastants
Cell,Vol.112,293–301,February7,2003

28. 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

29. painless, a Drosophila
Gene Essential for
Nociception
Cell2003113:261–273

30. A Drosophila Mechanosensory
Transduction Channel
SCIENCE VOL 287 24 MARCH
2000 pp. 2229-2234

31. Two interdependent TRPV channel
subunits, Inactive and Nanchung,
mediate hearing in Drosophila.

32. A TRPV family ion channel required for
hearing in Drosophila.
NATURE | VOL 424 | 3 JULY 2003 | pp. 81-84

33. Mechanotransduction in vertebrate hair
cells.
Nat Rev Neurosci 2008. no. 8: pp. 510–521

34. TRPN channel (NOMPC) is activated by
mechanical stimulation on a microsecond
time scale (~650 μs)
Neuron 67, 381–391, August 12, 2010

35. TRP channels and diseases.
Eur J Physiol (2011) 461:499–506
Eur J Physiol (2010) 460:437–450

36. The neurodegeneration resulted from
impaired clearance of early apoptotic
neurons
Cell 135, 838–851, November 28, 2008

37. 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.