The TRP superfamily

Members of the transient receptor potential (TRP) superfamily are cation channels that depolarise cells by allowing cations to flow into the cytoplasm down their electrochemical gradients either from extracellular sources or from the endoplasmic reticulum (ER) [1, 2]. The cation selectivity varies between TRPs [3]. In neurons transmembrane voltage (Vm) dictates action potential propagation, and muscle contraction [1]. In non-excitable cells Vm is a component of the electrochemical gradient which drives calcium entry through plasma membrane channels and controls the gating of voltage-dependent Ca2+, K+, and Cl channels [1]. Only two TRP channels are impermeable to Ca2+ [3]. Elevated cytoplasmic Ca2+ activates various signalling pathways leading to neurotransmitter release, cell proliferation, gene transcription, and apoptosis to name but a few [4].

The TRP superfamily comprises over 30 members and can be divided into seven families, six of which have human members [4]. The three largest families are TRPM, TRPV and TRPC. There are four smaller families consisting of TRPML, TRPP, TRPA and TRPN which is not expressed in mammals [4]. The human TRPM family comprises eight members that are genetically and functionally diverse and takes its name from Melastatin (TRPM1) which is used as a prognostic marker for melanoma metastasis [1]. TRPMs have diverse functional properties such as controlling Mg2+ entry, modulating the membrane potential, and sensing cold and menthol in sensory neurons [5]. The TRPV family comprises six members. The vanilloid receptor (TRPV1), the founding member is activated by a variety of signals including vanilloid compounds such as capsaicin, noxious signals, hypotonic cell swelling and heat. All TRPVs are activated by heat and may therefore function in thermosensation [4]. The mammalian TRPC family has seven members designated TRPC1-7 and are known to control neuronal growth cone guidance [1].

Refs

  1. Ramsey, I.S. Delling, M. Clapham, D.E. 2006. An introduction to TRP channels. Annual review of physiology. 68:619-647.
  2. Turner, H. Fleig, A. Stokes, A. Kinet, J.P. Penner, R. 2003. Discrimination of intracellular calcium store subcompartments using TRPV1 (transient receptor potential channel, vanilloid subfamily member 1) release channel activity. The biochemical journal. 371:341-350.
  3. Owsianik G, Talavera K, Voets T, Nilius B. 2006. Permeation and selectivity of TRP channels. Annual review of physiology. 68:685-717.
  4. Pedersen, S.F. Owsianik, G. Nilius, B. 2005. TRP channels: an overview. Cell Calcium. 38:233-252.
  5. Trebak, M. 2006. Canonical transient receptor potential channels in disease: targets for novel drug therapy? Drug discovery today. 11:924-930.
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