TRP channels: An overview

Pedersen, Stine Falsig; Owsianik, Grzegorz; Nilius, Bernd

doi:10.1016/j.ceca.2005.06.028

Cited by 689 publications

(621 citation statements)

References 250 publications

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“…The cells were sequentially perfused with solutions containing 140 or 0 mM Na þ , as indicated by the dark and light grey bars. Almost all TRP channels function as non-selective, Ca 2 þ -permeable channels (Pedersen et al, 2005;Nilius et al, 2007), and TRPML3(A419P) is permeable to Ca 2 þ (Grimm et al, 2007) and conducts Ca 2 þ at isotonic extracellular Ca 2 þ (Ca 2 þ o ) (Xu et al, 2007). Notably, Figures 1D (Owsianik et al, 2006), indicating that TRPML3 is a Ca 2 þ channel that is also permeable to monovalent cations.…”

Section: Resultsmentioning

confidence: 99%

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A novel mode of TRPML3 regulation by extracytosolic pH absent in the varitint-waddler phenotype

Kim

Tjon-Kon-Sang

et al. 2008

EMBO J

140

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TRPML3 belongs to the TRPML subfamily of the transient receptor potential (TRP) channels. The A419P mutation in TRPML3 causes the varitint-waddler phenotype as a result of gain-of-function mutation (GOF). Regulation of the channels and the mechanism by which the A419P mutation leads to GOF are not known. We report here that TRPML3 is a Ca 2 þ -permeable channel with a unique form of regulation by extracytosolic (luminal) H þ (H þ e-cyto ). Regulation by H þ e-cyto is mediated by a string of three histidines (H252, H273, H283) in the large extracytosolic loop between transmembrane domains (TMD) 1 and 2. Each of the histidines has a unique role, whereby H252 and H273 retard access of H þ e-cyto to the inhibitory H283. Notably, the H283A mutation has the same phenotype as A419P and locks the channel in an open state, whereas the H283R mutation inactivates the channel. Accordingly, A419P eliminates regulation of TRPML3 by H þ e-cyto , and confers full activation to TRPML3(H283R). Activation of TRPML3 and regulation by H þ e-cyto are altered by both the a-helix-destabilizing A419G and the a-helixfavouring A419M and A419K. These findings suggest that regulation of TRPML3 by H þ e-cyto is due to an effect of the large extracytosolic loop on the orientation of fifth TMD and thus pore opening and show that the GOF of TRPML3(A419P) is due to disruption of this communication.

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Section: Resultsmentioning

confidence: 99%

“…TRPML3 is an ion channel that belongs to the TRPML subfamily of the transient receptor potential (TRP) cation channels superfamily (Pedersen et al, 2005). The TRPML subfamily has three members, TRPML1, TRPML2 and TRPML3.…”

Section: Introductionmentioning

confidence: 99%

A novel mode of TRPML3 regulation by extracytosolic pH absent in the varitint-waddler phenotype

Kim

Tjon-Kon-Sang

et al. 2008

EMBO J

140

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“…Taken together, these data suggest that PACSIN 3 acts as an auxiliary protein of TRPV4 channel that not only affects the channel's subcellular localization but also modulates its function in a stimulus-specific manner. TRPV4 2 is a Ca 2ϩ -and Mg 2ϩ -permeable non-selective cation channel of the vanilloid-type transient receptor potential (TRPV) channel subfamily (1)(2)(3)(4)(5)(6)(7). Like other TRP channels, it has six transmembrane-spanning (TM) domains with a putative pore region between TM5 and TM6, and cytoplasmic N and C termini (8,9).…”

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confidence: 99%

Stimulus-specific Modulation of the Cation Channel TRPV4 by PACSIN 3

D’hoedt

Owsianik

Prenen

et al. 2008

Journal of Biological Chemistry

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116

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TRPV4, a member of the vanilloid subfamily of the transient receptor potential (TRP) channels, is activated by a variety of stimuli, including cell swelling, moderate heat, and chemical compounds such as synthetic 4␣-phorbol esters. TRPV4 displays a widespread expression in various cells and tissues and has been implicated in diverse physiological processes, including osmotic homeostasis, thermo-and mechanosensation, vasorelaxation, tuning of neuronal excitability, and bladder voiding. The mechanisms that regulate TRPV4 in these different physiological settings are currently poorly understood. We have recently shown that the relative amount of TRPV4 in the plasma membrane is enhanced by interaction with the SH3 domain of PACSIN 3, a member of the PACSIN family of proteins involved in synaptic vesicular membrane trafficking and endocytosis. Here we demonstrate that PACSIN 3 strongly inhibits the basal activity of TRPV4 and its activation by cell swelling and heat, while leaving channel gating induced by the synthetic ligand 4␣-phorbol 12,13-didecanoate unaffected. A single proline mutation in the SH3 domain of PACSIN 3 abolishes its inhibitory effect on TRPV4, indicating that PACSIN 3 must bind to the channel to modulate its function. In line herewith, mutations at specific proline residues in the N terminus of TRPV4 abolish binding of PACSIN 3 and render the channel insensitive to PACSIN 3-induced inhibition. Taken together, these data suggest that PACSIN 3 acts as an auxiliary protein of TRPV4 channel that not only affects the channel's subcellular localization but also modulates its function in a stimulus-specific manner.TRPV4 2 is a Ca 2ϩ -and Mg 2ϩ -permeable non-selective cation channel of the vanilloid-type transient receptor potential (TRPV) channel subfamily (1-7). Like other TRP channels, it has six transmembrane-spanning (TM) domains with a putative pore region between TM5 and TM6, and cytoplasmic N and C termini (8,9). TRPV4 is expressed in a broad range of tissues, including the lung, spleen, testis, fat, brain, cochlea, skin, smooth muscle, kidney, liver, and vascular endothelium (1, 2, 10 -12). Due to its broad expression pattern and gating promiscuity, TRPV4 has the potential to play a role in diverse physiological processes (13). Indeed, using knockdown or knock-out strategies, a role for TRPV4 in osmotic homeostasis, thermosensing, pain, and vascular function has been firmly established (14 -19). However, little is known about the mechanisms that regulate TRPV4 function in these different physiological settings, and it is unclear whether all known activation mechanisms are operating in every TRPV4-expressing cell. Heterologously expressed TRPV4 can be activated by a broad range of physical and chemical stimuli, including osmotic cell swelling (1, 2, 4, 20, 21), moderate heat (12, 22), synthetic ligands stimuli as 4␣-phorbol 12,13-didecanoate (4␣-PDD) (13, 23), mechanical force (14, 19, 24 -26), fluid viscosity (27), and endogenous ligands such as anandamide and arachidonic acid (AA)-derived epo...

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“…L'impact fonctionnel des modifications pore-structure sur les propriétés des > Les canaux TRP (transient receptor potential) représentent une nouvelle grande famille qui comprend plus de 50 canaux perméables aux cations, exprimés de la levure à l'homme. Sur la base des homologies structurelles, cette famille est divisée en 7 groupes : TRPC [1][2][3][4][5][6][7] Canonique, TRPV [1][2][3][4][5][6] Vanilloïde, TRPM [1][2][3][4][5][6][7][8] Mélastatine, TRPP [1][2][3] Polycystine, TRPML Mucolipine, TRPA Ankyrine et les TRPN (nompC) non représentés chez les mammifères. Le clonage a permis la caractérisation de ces canaux peu dépendants du potentiel et présentant généralement une perméabilité non spécifique pour les cations.…”

Section: La Nouvelle Famille Des Canaux Trpunclassified

“…Les modifications du gradient sodique vont intercanaux TRP a été récemment résumé [5]. Les canaux TRP sont activés de façon très variée par des messagers intra-ou extracellulaires, des composés chimiques, des stimulations mécaniques ou un stress osmotique [6,7]. …”

Section: Les Canaux Trpc Canoniquesunclassified

Les canaux TRP(transient receptor potential)

Vassort

Fauconnier

2008

Med Sci (Paris)

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Les canaux ioniques, et particulièrement ceux qui sont perméables au Ca 2+ , occupent une position majeure dans le contrôle des activités cellulaires que relaient les changements de la concentration calcique intracellulaire. Les études électrophysiologiques et de fluorescence ont permis de distinguer les canaux calciques directement activés par le potentiel et dont l'identité moléculaire et la structure tridimensionnelle sont maintenant bien connues, de ceux qui sont activés par la stimulation des récepteurs (receptoroperated channel, ROC) ou la déplétion des réservoirs calciques intracellulaires (store-operated channel, SOC). La nouvelle famille des canaux TRPTout récemment est apparue une superfamille très variée de canaux perméables aux cations et présents dans la plupart des types cellulaires des mammifères, les canaux TRP. L'archétype de ce canal a été découvert chez Drosophila melanogaster où il joue un rôle dans la phototransduction impliquant un signal calcique ; une mutation de son gène entraîne une réponse transitoire du potentiel bien que la lumière soit maintenue [1]. Chaque sous-unité TRP est constituée de six domaines transmembranaires avec un pore entre les cinquième et sixième segments transmembranaires, structure semblable à celle des canaux potassiques sensibles au potentiel (Figure 1). Comme ces derniers, les TRP s'assemblent en homo-ou hétéro-tétramères pour former un canal cationique non sélectif [2][3][4]. En fonction des homologies de leurs acides aminés, les TRP sont regroupés en 7 familles : TRPC, TRPM, TRPV, TRPA, TRPP, TRPML et TRPN. Aux 13 membres de cette superfamille de TRP décrits chez la drosophile correspondent 28 membres chez les mammifères où les TRPN ne sont pas représentés. Tous les canaux TRP sont perméables aux cations. La plupart sont perméables au Ca 2+ avec un rapport de perméabilité P Ca /P Na variant de 0,3 à 10. La structure du pore joue un rôle essentiel dans la perméabilité et la sélectivité d'un canal particulier. L'impact fonctionnel des modifications pore-structure sur les propriétés des

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TRP channels: An overview

Cited by 689 publications

References 250 publications

A novel mode of TRPML3 regulation by extracytosolic pH absent in the varitint-waddler phenotype

A novel mode of TRPML3 regulation by extracytosolic pH absent in the varitint-waddler phenotype

Stimulus-specific Modulation of the Cation Channel TRPV4 by PACSIN 3

Les canaux TRP(transient receptor potential)

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