RhoA Interaction with Inositol 1,4,5-Trisphosphate Receptor and Transient Receptor Potential Channel-1 Regulates Ca2+ Entry

Mehta, Dolly; Ahmmed, Gias U.; Paria, Biman C.; Holinstat, Michael; Voyno-Yasenetskaya, Tatyana A.; Tiruppathì, Chinnaswamy; Minshall, Richard D.; Malik, Asrar B.

doi:10.1074/jbc.m302401200

Cited by 198 publications

(195 citation statements)

References 64 publications

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“…This is consistent with the activation of a small GTP-binding protein that regulates vesicle trafficking and fusion to the plasma membrane (45). Proteins from the Rho GTPase family, which are involved in the regulation of endocytotic and exocytotic pathways (46), have been implicated in the regulation of Ca 2ϩ entry in several cell systems (31,(47)(48)(49)(50)(51)(52). Also, in Xenopus oocytes and HEK 293 cells negative modulation of the soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) complex significantly inhibited store-operated Ca 2ϩ entry and I SOC , suggesting that an intact SNARE complex and a process of membrane fusion are required for Ca 2ϩ entry (31,53).…”

Section: Discussionmentioning

confidence: 59%

Exocytotic Insertion of TRPC6 Channel into the Plasma Membrane upon Gq Protein-coupled Receptor Activation

Cayouette¹,

Lussier

Mathieu

et al. 2004

Journal of Biological Chemistry

171

126

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TRPC proteins are the mammalian homologues of the Drosophila transient receptor potential channel and are involved in calcium entry after agonist stimulation of non-excitable cells. Seven mammalian TRPCs have been cloned, and their mechanisms of activation and regulation are still the subject of intense research. TRPC proteins interact with the inositol 1,4,5-trisphosphate receptor, and the conformational coupling plays a critical role in the activation of calcium entry. Some evidence also supports an exocytotic mechanism as part of the activation of calcium entry. To investigate the possible involvement of exocytosis in TRPC6 activation, we evaluated the location of TRPC6 at the plasma membrane by biotinylation labeling of cell surface proteins and by indirect immunofluorescence marking of TRPC6 in stably transfected HEK 293 cells. We showed that when the muscarinic receptor was stimulated or the thapsigargin-induced intracellular calcium pool was depleted the level of TRPC6 at the plasma membrane increased. The carbachol concentration at which TRPC6 externalization occurred was lower than the concentration required to activate TRPC6. Externalization occurred within the first 30 s of stimulation, and TRPC6 remained at the plasma membrane as long as the stimulus was present. These results indicate that an exocytotic mechanism is involved in the activation of TRPC6.Increases in intracellular calcium ([Ca 2ϩ ] i ) regulate important cellular functions, including cell growth, differentiation, contraction, and secretion (1, 2). The increase in [Ca 2ϩ ] i is initiated by the activation of phospholipase C␤ or -␥ by a G q protein-coupled receptor or tyrosine kinase receptor, respectively, causing the hydrolysis of phosphatidylinositol 4,5-bisphosphate and generating two-second messengers, inositol 1,4,5-trisphosphate (IP 3 ) 1 and diacylglycerol. IP 3 binds to its specific receptor on the endoplasmic reticulum and causes the first phase of Ca 2ϩ mobilization by releasing Ca 2ϩ from the intracellular pool. The second phase involves Ca 2ϩ entry through the plasma membrane, which maintains [Ca 2ϩ ] i above basal levels. No cellular activity has ever been observed in the absence of this second phase of Ca 2ϩ mobilization.The TRPC protein family is involved in Ca 2ϩ entry (3-5). Seven genes have been identified in the mammalian genome by homology with Drosophila TRP and TRPL, two proteins that are responsible for the light-induced current in insect phototransduction. TRPC channels are probably composed of four subunits, each containing three to four ankyrin-like repeats, two predicted coiled-coil regions (one in the amino terminus and another one in the carboxyl terminus), and a membranespanning region. The amino acids that link the fifth and sixth transmembrane segments form the putative pore region loop. Recent studies on the subunit arrangement of native TRPC in rat brain synaptosomes and the overexpression of TRPC in various systems suggest that the TRPC protein family can be subdivided in two distinct groups and that...

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Section: Discussionmentioning

confidence: 59%

Exocytotic Insertion of TRPC6 Channel into the Plasma Membrane upon Gq Protein-coupled Receptor Activation

Cayouette¹,

Lussier

Mathieu

et al. 2004

Journal of Biological Chemistry

171

126

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“…For the most part, receptormediated translocation of TRPC channels has been studied with over-expressed TRPC channels. Receptor-stimulated translocation of TRPC1 was reported to be dependent on the small GTP-binding protein RhoA, [48], which is a regulator of vesicle trafficking and exocytosis. Similarly, stimulation of the M3 receptor results in translocation of TRPC3 [18,49] and requires the function of the SNARE protein VAMP2 [49].…”

Section: Homer1 and Translocation Of Trpc Channelsmentioning

confidence: 99%

Homer proteins in Ca2+ signaling by excitable and non-excitable cells

et al. 2007

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Homers are scaffolding proteins that bind Ca 2+ signaling proteins in cellular microdomains. The Homers participate in targeting and localization of Ca 2+ signaling proteins in signaling complexes. However, recent work showed that the Homers are not passive scaffolding proteins, but rather they regulate the activity of several proteins within the Ca 2+ signaling complex in an isoform specific manner. Homer2 increases the GAP activity of RGS proteins and PLCβ that accelerate the GTPase activity of Gα subunits. Homer1 gates the activity of TRPC channels, controls the rates of their translocation and retrieval from the plasma membrane and mediates the conformational coupling between TRPC channels and IP 3 Rs. Homer1 stimulates the activity of the cardiac and neuronal Ltype Ca 2+ channels Ca v 1.2 and Ca v 1.3. Homer1 also mediates the communication between the cardiac and smooth muscle ryanodine receptor RyR2 and Ca v 1.2 to regulate E-C coupling. In many cases the Homers function as a buffer to reduce the intensity of Ca 2+ signaling and create a negative bias that can be reversed by the immediate early gene form of Homer 1. Hence, the Homers should be viewed as the buffers of Ca 2+ signaling that ensure a high spatial and temporal fidelity of the Ca 2+ signaling and activation of downstream effects.

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“…In this context, the recent interest in human 'transportome' involvement in tumour vascularization is a promising field, because several members are activated downstream of the recruitment of VEGF receptors. For example, whereas the interference with the bulk VEGF signalling alters the activity of a multitude of different cells and functions, targeting TRPC6 or Orai1 may affect only EC migration and proliferation [31,34,44,53,92], whereas TRPC1 and STIM1 may selectively influence vascular permeability [56][57][58]61].…”

Section: Resultsmentioning

confidence: 99%

“…Other groups reported a role of VEGF-mediated SOCE owing to TRPC1 in the enhancement of HMVEC and HUVEC permeability [56][57][58]. Remarkably, TRPC1 is proangiogenic in vivo: knockdown of zebrafish TRPC1 by morpholinos caused severe angiogenic defects in intersegmental vessel sprouting, presumably owing to impaired filopodia extension during EC migration [62] (table 1 and figure 2).…”

Section: Transient Receptor Potential Proteins and Stim1-orai1 Complexmentioning

confidence: 99%

Functional properties of ion channels and transporters in tumour vascularization

Fiorio

Munaron

2014

Phil. Trans. R. Soc. B

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Vascularization is crucial for solid tumour growth and invasion, providing metabolic support and sustaining metastatic dissemination. It is now accepted that ion channels and transporters play a significant role in driving the cancer growth at all stages. They may represent novel therapeutic, diagnostic and prognostic targets for anti-cancer therapies. On the other hand, although the expression and role of ion channels and transporters in the vascular endothelium is well recognized and subject of recent reviews, only recently has their involvement in tumour vascularization been recognized. Here, we review the current literature on ion channels and transporters directly involved in the angiogenic process. Particular interest will be focused on tumour angiogenesis in vivo as well as in the different steps that drive this process in vitro , such as endothelial cell proliferation, migration, adhesion and tubulogenesis. Moreover, we compare the ‘transportome’ system of tumour vascular network with the physiological one.

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RhoA Interaction with Inositol 1,4,5-Trisphosphate Receptor and Transient Receptor Potential Channel-1 Regulates Ca2+ Entry

Cited by 198 publications

References 64 publications

Exocytotic Insertion of TRPC6 Channel into the Plasma Membrane upon Gq Protein-coupled Receptor Activation

Exocytotic Insertion of TRPC6 Channel into the Plasma Membrane upon Gq Protein-coupled Receptor Activation

Homer proteins in Ca2+ signaling by excitable and non-excitable cells

Functional properties of ion channels and transporters in tumour vascularization

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