AbstractsPosted by Md. Shahidul Islam Mon, February 07, 2011 19:21:39
TRP Channels in Parasites
Adrian J. Wolstenholme, Sally M. Williamson, and Barbara J. Reaves
A wide range of single- and multi-cellular parasites infect humans and other animals, causing some of the most prevalent and debilitating diseases on the planet. There have been virtually no published studies on the TRP channels of this diverse group of organisms. However, since many parasite genomes have been sequenced, it is simple to demonstrate that they are present in all parasitic metazoans and that sequences related to the yeast trp are present in many protozoans, including all the kinetoplastids.We compared the TRP genes of three species of animal and plant parasitic nematode to those of C. elegans and found that the parasitic species all had fewer such genes. These differences may reflect the phylogenetic distance between the species studied, or may be due to loss of specific gene functions following the evolution of the parasitic lifestyle. Other helminth groups, the trematodes and cestodes, seem to possess many TRPC and TRPM genes, but lack TRPV and TRPN. Most ectoparasites are insects or arachnids. We compared the TRP genes of a plant parasitic aphid and an animal parasite louse and tick with those of Drosophila. Again, all the parasitic species seemed to have fewer types of TRP channel, though the difference was less marked than for the nematodes. The aphid lacks TRPP and TRPML channel genes, whereas the tick lacked those encoding TRPVs. Again, these differences may reflect adaptation to parasitism, and could enable TRP channels to be targeted in the development of novel antiparasitic drugs.
AbstractsPosted by Md. Shahidul Islam Mon, February 07, 2011 19:15:02
Receptor Signaling Integration by TRP Channelsomes
Yasuo Mori, Taketoshi Kajimoto, Akito Nakao, Nobuaki Takahashi, and Shigeki Kiyonaka
Homologues of transient receptor potential (TRP) genes encode a variety of cation channels, most of which conduct Ca2+ across the plasma membrane. TRP proteins interact with a variety of proteins and other biologically important factors, such as second messengers, and thereby form "channelsomes", most of which function as Ca2+ signalsomes. Activation mechanisms and final outputs are exquisitely incorporated in the signaling system of TRP channelsomes. In this study, we discuss the channelsomes of TRPC3, TRPC5, and TRPM2, which show unique molecular interactions and modulations of activation. Comparative studies of these specific TRP channelsomes should aid the determination of general rules that govern the formation and regulation of channelsomes and signalsomes.
AbstractsPosted by Md. Shahidul Islam Mon, February 07, 2011 18:58:55
Gating Mechanisms of Canonical Transient Receptor Potential Channel Proteins: Role of Phosphoinositols and Diacylglycerol
Anthony P. Albert
Canonical transient receptor potential (TRPC) Ca2+-permeable channels are members of the mammalian TRP super-family of cation channels, and have the closest homology to the founding members, TRP and TRPL, discovered in Drosophila photoreceptors. The TRPC subfamily is composed of 7 subunits (C1–C7, with TRPC2 a pseudogene in humans), which can all combine with one another to form homomeric and heteromeric structures. This review focuses on mechanisms involved in opening TRPC channels (i.e. gating mechanisms). It initially describes work on the involvement of phosphatidylinositol-4,5-bisphosphate (PIP2) and diacylglycerol (DAG) in gating TRP and TRPL channels in Drosophila, and then discusses evidence that similar gating mechanisms are involved in opening mammalian TRPC channels. It concludes that there are two common activation pathways of mammalian TRPC channels. Non-TRPC1-containing channels are opened by interactions between DAG, the direct activating ligand, and PIP2, which acts as a physiological antagonist at TRPC proteins. Competitive interactions between an excitatory effect of DAG and an inhibitory action of PIP2 can also be modulated by IP3 acting via an IP3 receptor-independent mechanism. In contrast TRPC1-containing channels are gating by PIP2, which requires PKC-dependent phosphorylation of TRPC1 proteins.
AbstractsPosted by Md. Shahidul Islam Mon, February 07, 2011 17:56:01
The TRPC Ion Channels: Association with Orai1 and STIM1 Proteins and Participation in Capacitative and Non-capacitative Calcium Entry
Gines M. Salido, Isaac Jardín, and Juan A. Rosado
Transient receptor potential (TRP) proteins are involved in a large number of non-selective cation channels that are permeable to both monovalent and divalent cations. Two general classes of receptor-mediated Ca2+ entry has been proposed: one of then is conduced by receptor-operated Ca2+ channels (ROC), the second is mediated by channels activated by the emptying of intracellular Ca2+ stores (store-operated channels or SOC). TRP channels have been presented as subunits of both ROC and SOC, although the precise mechanism that regulates the participation of TRP proteins in these Ca2+ entry mechanisms remains unclear. Recently, TRPC proteins have been shown to associate with Orai1 and STIM1 in a dynamic ternary complex regulated by the occupation of membrane receptors in several cell models, which might play an important role in the function of TRPC proteins. The present review summarizes the current knowledge concerning the association of TRP proteins with Orai and STIM proteins and how this affects the participation of TRP proteins in store-operated or receptor-operated Ca2+ entry.
AbstractsPosted by Md. Shahidul Islam Mon, February 07, 2011 17:48:24
Contribution of TRPC1 and Orai1 to Ca2+ Entry Activated by Store Depletion
Kwong Tai Cheng, Hwei Ling Ong, Xibao Liu, and Indu S. Ambudkar
Store-operated Ca2+ entry (SOCE) is activated in response to depletion of the ER-Ca2+ stores by the ER Ca2+ sensor protein, STIM1 which oligomerizes and moves to ER/PM junctional domains where it interacts with and activates channels involved in SOCE. Two types of channel activities have been described. ICRAC, via Ca2+ release-activated Ca2+ (CRAC) channel, which displays high Ca2+ selectivity and accounts for the SOCE and cell function in T lymphocytes, mast cells, platelets, and some types of smooth muscle and endothelial cells. Orai1 has been established as the pore-forming component of CRAC channels and interaction of Orai1 with STIM1 is sufficient for generation of the CRAC channel. Store depletion also leads to activation of relatively non-selective cation currents (referred to as ISOC) that contribute to SOCE in several other cell types. TRPC channels, including TRPC1, TRPC3, and TRPC4, have been proposed as possible candidate channels for this Ca2+ influx. TRPC1 is the best characterized channel in this regard and reported to contribute to endogenous SOCE in many cells types. TRPC1-mediated Ca2+ entry and cation current in cells stimulated with agonist or thapsigargin are inhibited by low [Gd3+] and 10–20 μM 2APB (conditions that block SOCE). Importantly, STIM1 also associates with and gates TRPC1 via electrostatic interaction between STIM1 (684KK685) and TRPC1 (639DD640). Further, store depletion induces dynamic recruitment of a TRPC1/STIM1/Orai1 complex and knockdown of Orai1 completely abrogates TRPC1 function. Despite these findings, there has been much debate regarding the activation of TRPC1 by store depletion as well as the role of Orai1 and STIM1 in SOC channel function. This chapter summarizes recent studies and concepts regarding the contributions of Orai1 and TRPC1 to SOCE. Major unresolved questions regarding functional interaction between Orai1 and TRPC1 as well as possible mechanisms involved in the regulation of TRPC channels by store depletion will be discussed.
AbstractsPosted by Md. Shahidul Islam Mon, February 07, 2011 17:27:41
Primary Thermosensory Events in Cells
Temperature sensing is essential for the survival of living organisms. Since thermal gradients are almost everywhere, thermoreception could represent one of the oldest sensory transduction processes that evolved in organisms. There are many examples of temperature changes affecting the physiology of living cells. Almost all classes of biological macromolecules in a cell (nucleic acids, lipids, proteins) can serve as a target of the temperature-related stimuli. This review is devoted to some common features of different classes of temperature-sensing molecules as well as molecular and biological processes involved in thermosensation. Biochemical, structural and thermodynamic approaches are discussed in order to overview the existing knowledge on molecular mechanisms of thermosensation.
AbstractsPosted by Md. Shahidul Islam Mon, February 07, 2011 17:20:28
Thermo-TRP Channels: Biophysics of Polymodal Receptors
David Baez-Nieto, Juan Pablo Castillo, Constantino Dragicevic, Osvaldo Alvarez, and Ramon Latorre
In this chapter we discuss the polymodal activation of thermo-TRP channels using as exemplars two of the best characterized members of this class of channels: TRPM8 and TRPV1. Since channel activation by temperature is the hallmark of thermo-TRP channels, we present a detailed discussion on the thermodynamics involved in the gating processes by temperature, voltage, and agonists. We also review recently published data in an effort to put together all the pieces available of the amazing puzzle of thermo-TRP channel activation. Special emphasis is made in the structural components that allow the channel-forming proteins to integrate such diverse stimuli, and in the coupling between the different sensors and the ion conduction pathway. We conclude that the present data is most economically explained by allosteric models in which temperature, voltage, and agonists act separately to modulate channel activity.
AbstractsPosted by Md. Shahidul Islam Mon, February 07, 2011 17:13:31
Complex Regulation of TRPV1 and Related Thermo-TRPs: Implications for Therapeutic Intervention
Rosa Planells-Cases, Pierluigi Valente, Antonio Ferrer-Montiel, Feng Qin, and Arpad Szallasi
The capsaicin receptor TRPV1 (Transient Receptor Potential, Vanilloid family member 1), the founding member of the heat-sensitive TRP ("thermo-TRP") channel family, plays a pivotal role in pain transduction. There is mounting evidence that TRPV1 regulation is complex and is manifest at many levels, from gene expression through post-translational modification and formation of receptor heteromers to subcellular compartmentalization and association with regulatory proteins. These mechanisms are believed to be involved both in disease-related changes in TRPV1 expression, and the long-lasting refractory state, referred to as "desensitization", that follows TRPV1 agonist treatment. The signaling cascades that regulate TRPV1 and related thermo-TRP channels are only beginning to be understood. Here we review our current knowledge in this rapidly changing field. We propose that the complex regulation of TRPV1 may be exploited for therapeutic purposes, with the ultimate goal being the development of novel, innovative agents that target TRPV1 in diseased, but not healthy, tissues. Such compounds are expected to be devoid of the side-effects (e.g. hyperthermia and impaired noxious heat sensation) that plague the clinical use of existing TRPV1 antagonists.