| Literature References | 1. ZHU, X., JIANG, M., PEYTON, M., BOULAY, G., HURST, R., STEFANI, E.
AND BIRNBAUMER, L.
Trp, a novel mammalian gene family essential for agonist-activated
capacitative Ca2+ entry.
CELL 85 661-671 (1996).
2. BOULAY, G., ZHU, X., PEYTON, M., JIANG, M., HURST, R., STEFANI, E.
AND BIRNBAUMER, L.
Cloning and expression of a novel mammalian homolog of Drosophila transient
receptor potential (Trp) involved in calcium entry secondary to activation
of receptors coupled by the Gq class of G protein.
J.BIOL.CHEM. 272 29672-29680 (1997).
3. CLAPHAM, D., RUNNELS, L. AND STRUBING, C.
The TRP ion channel family.
NAT.REV.NEUROSCI. 2 6387-396 (2001).
4. HARTENECK, C., PLANT, T. AND SCHULTZ, G.
From worm to man: three subfamilies of TRP channels.
TRENDS NEUROSCI. 23 159-166 (2000).
5.PHILIPP, S., HAMBRECHT, J., BRASLAVSKI, L., SCHROTH, G., FREICHEL, M.,
MURAKAMI, M., CAVALIE, A. AND FLOCKERZI, V.
A novel capacitative calcium entry channel expressed in excitable cells.
EMBO J. 17 4274-4282 (1998).
6. SCHAEFER, M., PLANT, T., OBUKHOV, A., HOFMANN, T., GUDERMANN, T. AND
SCHULTZ, G.
Receptor-mediated regulation of the nonselective cation channels TRPC4 and
TRPC5.
J.BIOL.CHEM. 275 17517-17526 (2000).
7. STRUBING, C., KRAPIVINSKY, G., KRAPIVINSKY, L. AND CLAPHAM, D.
TRPC1 and TRPC5 form a novel cation channel in mammalian brain.
NEURON 29 645-655 (2001).
|
| Documentation | Transient receptor potential (Trp) and related proteins are thought to be
Ca2+ ion channel subunits that mediate capacitative Ca2+ entry in response
to a range of external and internal cell stimuli. Such Ca2+ entry is thought
to be an essential component of cellular responses to many hormones and
growth factors, and acts to replenish intracellular Ca2+ stores that have
been emptied through the action of inositol triphosphate (IP3) and other
agents. In non-excitable cells, i.e. those that lack voltage-gated Ca2+
channels, such as hepatocytes, this mode of Ca2+ entry is thought to be an
important step in generating the oscillations of intracellular Ca2+
concentration that characterise their response to stimulatory agents [1].
Studies on the visual transduction system in Drosophila led to the molecular
cloning of Trp and the cDNA of a related protein, Trp-like, which show
similarity to voltage gated Ca2+ channels in the regions known as S3 through
S6, including the S5-S6 linker that forms the ion-selective channel pore [2].
This provided evidence that Trp and/or related proteins might form mammalian
capacitative Ca2+ entry channels.
A number of Trp and Trp-like channel gene isoforms have now been cloned,
including several mammalian homologues. The Trp family is thought to encode
at least 20 Ca2+-permeable channel proteins. Hydropathy analysis suggests
that they share a common transmembrane (TM) topology. Each family member is
predicted to possess 6 TM domains with intracellular N- and C-termini, which
is similar to the core structure of the pore-forming subunits of the voltage
-gated Na+ and Ca2+ channels. By analogy with these proteins, which have
4 linked domains of 6 TM segments, it is likely that Trp channels are
homo- or heterotetramers of 4 single subunits [3].
The Trp family can be divided on the basis of sequence similarity into 3
subfamilies: short (S), long (L) and osm-like (O) Trp channels [4]. The
STrp subfamily includes Drosophila Trp and Trpl-like, and the mammalian
homologues TrpC1-7. Channels of the STrpC subfamily are activated following
receptor-mediated stimulation of different isoforms of phospholipase C [4].
TrpC5 was originally cloned from rabbit and mouse tissues [5]; a human
isoform has also been identified. Expression studies have demonstrated that
TrpC5 is able to form homomeric cation channels that are activated following
stimulation of Gq-coupled receptors and by receptor tyrosine kinases [6]. In
mammalian brain, TrpC5 has been reported to form heteromers with TrpC1,
which appear to be activated by Gq-linked receptors, but not by store
depletion [7]. This has led to the proposal that different TrpC heteromers
may form diverse receptor-regulated channels.
TRPCHANNEL5 is a 6-element fingerprint that provides a signature for
transient receptor potential channel 5. The fingerprint was derived from an
initial alignment of 3 sequences: the motifs were drawn from conserved
regions spanning virtually the full alignment length, focusing on those
sections that characterise TrpC5 but distinguish it from other family
members - motif 1 lies in the intracellular N-terminal region; motif 2
encodes the second half of TM domain 1; and motifs 3-6 reside within the
C-terminal cytoplasmic region. A single iteration on SPTR40_18f was required
to reach convergence, no further sequences being identified beyond the
starting set.
|