共查询到20条相似文献,搜索用时 15 毫秒
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Walker JK Gainetdinov RR Mangel AW Caron MG Shetzline MA 《American journal of physiology. Gastrointestinal and liver physiology》2000,279(2):G311-G318
The mechanisms by which dopamine (DA) influences gastrointestinal (GI) tract motility are incompletely understood and complicated by tissue- and species-specific differences in dopaminergic function. To improve the understanding of DA action on GI motility, we used an organ tissue bath system to characterize motor function of distal colonic smooth muscle segments from wild-type and DA transporter knockout (DAT -/-) mice. In wild-type mice, combined blockade of D(1) and D(2) receptors resulted in significant increases in tone (62 +/- 9%), amplitude of spontaneous phasic contractions (167 +/- 24%), and electric field stimulation (EFS)-induced (40 +/- 8%) contractions, suggesting that endogenous DA is inhibitory to mouse distal colonic motility. The amplitudes of spontaneous phasic and EFS-induced contractions were lower in DAT -/- mice relative to wild-type mice. These differences were eliminated by combined D(1) and D(2) receptor blockade, indicating that the inhibitory effects of DA on distal colonic motility are potentiated in DAT -/- mice. Motility index was decreased but spontaneous phasic contraction frequency was enhanced in DAT -/- mice relative to wild-type mice. The fact that spontaneous phasic and EFS-induced contractile activity were altered by the lack of the DA transporter suggests an important role for endogenous DA in modulating motility of mouse distal colon. 相似文献
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The transient receptor potential protein homologue TRPC5 was reported as a molecular identity for the muscarinic receptor-activated nonselective cationic channel (NSCC) in the murine stomach smooth muscle. The canonical, or classical, transient receptor potential proteins, TRPC4 and TRPC5, were suggested as members of the same subfamily of TRPC channels and to be coexpressed as a heteromultimer of both TRPC as well as a homotetramer of each TRPC protein. Thus, we investigated whether the TRPC4 channel is also responsible for the NSCC activated by acetylcholine (ACh) or carbachol (CCh) using electrophysiological techniques. The TRPC channels were expressed in HEK293 cells. When murine TRPC4 channels (mTRPC4) were expressed, the current–voltage relationship of mTRPC4 was also similar to that recorded in native murine gastric myocytes or mTRPC5-expressing HEK cells. With 0.2 mM GTPγS in the pipette solution, the currents in mTRPC4-expressing cells were activated transiently like those in NSCC in the murine stomach and the expressed mTRPC5. The currents recorded in mTRPC4-expressing cells were inhibited by 1 mM La3+ and 100 μM flufenamate. The currents recorded in mTRPC4-expressing cells depended on the extracellular calcium concentration. From the above results, we suggest that mTRPC4/5 might be candidates for the NSCC activated by ACh or CCh in the murine stomach. 相似文献
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Min Chen Jia Liu Hanjiang Luo Chunli Duan Ge Gao Hui Yang 《Journal of cellular and molecular medicine》2022,26(19):5008
Olfactory impairment is an initial non‐motor symptom of Parkinson''s disease that causes the deposition of aggregated α‐synuclein (α‐syn) in olfactory neurons. Transient receptor potential canonical (TRPC) channels are a diverse group of non‐selective Ca2+ entry channels involved in the progression or pathogenesis of PD via Ca2+ homeostatic regulation. However, the relationship between TRPC and α‐syn pathology in an olfactory system remains unclear. To address this issue, we assessed the olfactory function in α‐syn transgenic mice. In contrast with control mice, the transgenic mice exhibited impaired olfaction, TRPC3 activation and apoptotic neuronal cell death in the olfactory system. Similar results were observed in primary cultures of olfactory neurons, that is TRPC3 activation, increasing intracellular Ca2+ concentration and apoptotic cell death in the α‐syn‐overexpressed neurons. These changes were significantly attenuated by TRPC3 knockdown. Therefore, our findings suggest that TRPC3 activation and calcium dyshomeostasis play a key role in α‐syn‐induced olfactory dysfunction in mice. 相似文献
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Yanna Zhao Jiefeng Huang Tianyi Li Shuijuan Zhang Chengping Wen Lipei Wang 《Journal of cellular and molecular medicine》2022,26(4):1060
Berberine (BBR), an isoquinoline alkaloid, is used to treat gastrointestinal disorders as an herbal medicine in China. The aim of this study was to investigate the anti‐inflammatory activities of BBR in a mouse model with acute graft‐versus‐host disease (aGVHD). Mice were intravenously injected with bone marrow cells from donors combined with splenocytes to develop aGVHD. The body weight, survival rate and clinical scores were monitored. Then the levels of inflammatory cytokines, histological changes (lung, liver and colon), colonic mucosal barrier and gut microbiota were analysed. Moreover, the toll‐like receptor 4 (TLR4)/myeloid differentiation primary response gene 88 (Myd88)/nuclear factor‐κB signalling pathway, NLRP3 inflammasome and its cytokines’ expressions were determined. The results showed that the gavage of BBR lessened GVHD‐induced weight loss, high mortality and clinical scores, inhibited inflammation and target organs damages and prevented GVHD‐indued colonic barrier damage. Additionally, BBR modulated gut microbiota, suppressed the activation of the TLR4 signaling pathway and inhibited NLRP3 inflammasome and its cytokine release. This study indicated that BBR might be a potential therapy for aGVHD through NLRP3 inflammasome inhibition. 相似文献
7.
The effect of the selective 5-hydroxytryptamine (5-HT)(3) receptor agonist YM-31636 (2-(1H-imidazol-4-ylmethyl)-8H-indeno[1,2-d]thiazole monofumarate) on gut motility of fed ferrets was investigated. YM-31636 (0.1 mg/kg p.o.) induced a giant migrating contraction (GMC)-like, high-amplitude, ungrouped colonic contraction although it did not change the basal colonic motility pattern. This GMC-like contraction was always accompanied by defecation. Both GMC-like contraction and defecation were inhibited with the selective 5-HT(3) receptor antagonist ramosetron. YM-31636 affected gastric, duodenal and ileal motility pattern only slightly. These results suggest that 5-HT(3) receptor agonists such as YM-31636 are useful in treating constipation since they facilitate GMC-like contractions and defecation without undesired changes in gut motility pattern. 相似文献
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Nathalie Vaes Simone L Schonkeren Glenn Rademakers Amy M Holland Alexander Koch Marion J Gijbels Tom G Keulers Meike de Wit Laura Moonen Jaleesa R M Van der Meer Edith van den Boezem Tim G A M Wolfs David W Threadgill Jeroen Demmers Remond J A Fijneman Connie R Jimenez Pieter Vanden Berghe Kim M Smits Kasper M A Rouschop Werend Boesmans Robert M W Hofstra Veerle Melotte 《EMBO reports》2021,22(6)
The N‐Myc Downstream‐Regulated Gene 4 (NDRG4), a prominent biomarker for colorectal cancer (CRC), is specifically expressed by enteric neurons. Considering that nerves are important members of the tumor microenvironment, we here establish different Ndrg4 knockout (Ndrg4 −/−) CRC models and an indirect co‐culture of primary enteric nervous system (ENS) cells and intestinal organoids to identify whether the ENS, via NDRG4, affects intestinal tumorigenesis. Linking immunostainings and gastrointestinal motility (GI) assays, we show that the absence of Ndrg4 does not trigger any functional or morphological GI abnormalities. However, combining in vivo, in vitro, and quantitative proteomics data, we uncover that Ndrg4 knockdown is associated with enlarged intestinal adenoma development and that organoid growth is boosted by the Ndrg4 −/− ENS cell secretome, which is enriched for Nidogen‐1 (Nid1) and Fibulin‐2 (Fbln2). Moreover, NID1 and FBLN2 are expressed in enteric neurons, enhance migration capacities of CRC cells, and are enriched in human CRC secretomes. Hence, we provide evidence that the ENS, via loss of Ndrg4, is involved in colorectal pathogenesis and that ENS‐derived Nidogen‐1 and Fibulin‐2 enhance colorectal carcinogenesis. 相似文献
9.
Differential alterations in tachykinin NK2 receptors in isolated colonic circular smooth muscle in inflammatory bowel disease and idiopathic chronic constipation 总被引:12,自引:0,他引:12
Inflammatory bowel disease (IBD) and idiopathic chronic constipation (ICC) are intestinal disorders which disrupt normal colonic motility. Enteric tachykinins are well-recognised to play a role in the motor control of the gut, and increased colonic levels of substance P are seen in IBD, whereas decreased levels have been reported in ICC. In this investigation, we have characterised the tachykinin receptor population of normal human colonic circular smooth muscle and examined any changes that occur in IBD and ICC. The selective tachykinin NK2 receptor agonist, [beta-Ala8]neurokinin A(4-10), caused concentration-dependent contractions in healthy tissues; neither NK1 receptor-selective nor NK3 receptor-selective agonists were contractile. In diseased preparations also, only [beta-Ala8]neurokinin A(4-10) caused contractions with EC50 values similar to health. The maximum contractile responses (Emax), however, were significantly decreased in both forms of IBD but significantly increased in ICC. The muscarinic acetylcholine receptor agonist, carbachol, also caused contractions in diseased tissues, but EC50 and Emax values were not significantly different from health. The differential changes in contractility found in IBD and ICC are specific to NK2 receptors, and may reflect the altered levels of substance P or other tachykinins found in these intestinal disorders. 相似文献
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Hanna M. Peltonen Genevieve Bart Miia S.H. Antikainen Karl E. Åkerman 《Biochemical and biophysical research communications》2009,385(3):408-412
Oscillations of intracellular Ca2+ provide a novel mechanism for sustained activation of cellular processes. Receptor-activated oscillations are mainly thought to occur through rhythmic IP3-dependent store discharge. However, as shown here in HEK293 cells 1 nM orexin-A (Ox-A) acting at OX1 receptors (OX1R) triggered oscillatory Ca2+ responses, requiring external Ca2+. These responses were attenuated by interference with TRPC3 channel (but not TRPC1/4) function using dominant negative constructs, elevated Mg2+ (a blocker of many TRP channels) or inhibition of phospholipase A2. These treatments did not affect Ca2+ oscillations elicited by high concentrations of Ox-A (100 nM) in the absence of external Ca2+. OX1R are thus able to activate TRPC(3)-channel-dependent oscillatory responses independently of store discharge. 相似文献
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Poteser M Graziani A Rosker C Eder P Derler I Kahr H Zhu MX Romanin C Groschner K 《The Journal of biological chemistry》2006,281(19):13588-13595
Canonical transient receptor potential proteins (TRPC) have been proposed to form homo- or heteromeric cation channels in a variety of tissues, including the vascular endothelium. Assembly of TRPC multimers is incompletely understood. In particular, heteromeric assembly of distantly related TRPC isoforms is still a controversial issue. Because we have previously suggested TRPC proteins as the basis of the redox-activated cation conductance of porcine aortic endothelial cells (PAECs), we set out to analyze the TRPC subunit composition of endogenous endothelial TRPC channels and report here on a redox-sensitive TRPC3-TRPC4 channel complex. The ability of TRPC3 and TRPC4 proteins to associate and to form a cation-conducting pore complex was supported by four lines of evidence as follows: 1) Co-immunoprecipitation experiments in PAECs and in HEK293 cells demonstrated the association of TRPC3 and TRPC4 in the same complex. 2) Fluorescence resonance energy transfer analysis demonstrated TRPC3-TRPC4 association, involving close proximity between the N terminus of TRPC4 and the C terminus of TRPC3 subunits. 3) Co-expression of TRPC3 and TRPC4 in HEK293 cells generated a channel that displayed distinct biophysical and regulatory properties. 4) Expression of dominant-negative TRPC4 proteins suppressed TRPC3-related channel activity in the HEK293 expression system and in native endothelial cells. Specifically, an extracellularly hemagglutinin (HA)-tagged TRPC4 mutant, which is sensitive to blockage by anti-HA-antibody, was found to transfer anti-HA sensitivity to both TRPC3-related currents in the HEK293 expression system and the redox-sensitive cation conductance of PAECs. We propose TRPC3 and TRPC4 as subunits of native endothelial cation channels that are governed by the cellular redox state. 相似文献
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Hazel ErkanCandag Amy Clarke Oleksandra Tiapko Mathias AF Gsell Thomas Stockner Klaus Groschner 《EMBO reports》2022,23(7)
Coordination of lipids within transient receptor potential canonical channels (TRPCs) is essential for their Ca2+ signaling function. Single particle cryo‐EM studies identified two lipid interaction sites, designated L1 and L2, which are proposed to accommodate diacylglycerols (DAGs). To explore the role of L1 and L2 in TRPC3 function, we combined structure‐guided mutagenesis and electrophysiological recording with molecular dynamics (MD) simulations. MD simulations indicate rapid DAG accumulation within both L1 and L2 upon its availability within the plasma membrane. Electrophysiological experiments using a photoswitchable DAG‐probe reveal potentiation of TRPC3 currents during repetitive activation by DAG. Importantly, initial DAG exposure generates a subsequently sensitized channel state that is associated with significantly faster activation kinetics. TRPC3 sensitization is specifically promoted by mutations within L2, with G652A exhibiting sensitization at very low levels of active DAG. We demonstrate the ability of TRPC3 to adopt a closed state conformation that features partial lipidation of L2 sites by DAG and enables fast activation of the channel by the phospholipase C‐DAG pathway. 相似文献
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Jae-Pyo Jeon Seung-Eon Roh Jinhong Wie Jinsung Kim Hana Kim Kyu-Pil Lee Dongki Yang Ju-Hong Jeon Nam-Hyuk Cho In-Gyu Kim David E. Kang Hyun Jin Kim Insuk So 《Cell calcium》2013
The ubiquitous transient receptor potential canonical (TRPC) channels function as non-selective, Ca2+-permeable channels. TRPC channels are activated by stimulation of Gαq-PLC-coupled receptors. Here, we report that TRPC4/TRPC5 can be activated by Gαi. We studied the essential role of Gαi subunits in TRPC4 activation and investigated changes in ion selectivity and pore dilation of the TRPC4 channel elicited by the Gαi2 subunit. Activation of TRPC4 by Gαi2 increased Ca2+ permeability and Ca2+ influx through TRPC4 channels. Co-expression of the muscarinic receptor (M2) and TRPC4 in HEK293 cells induced TRPC4-mediated Ca2+ influx. Moreover, both TRPC4β and the TRPC4β-Gαi2 signaling complex induced inhibition of neurite growth and arborization in cultured hippocampal neurons. Cells treated with KN-93, a CaMKII inhibitor, prevented TRPC4- and TRPC4-Gαi2Q205L-mediated inhibition of neurite branching and growth. These findings indicate an essential role of Gαi proteins in TRPC4 activation and extend our knowledge of the functional role of TRPC4 in hippocampal neurons. 相似文献
14.
E-Ching Ong Vasyl Nesin Courtney L. Long Chang-Xi Bai Jan L. Guz Ivaylo P. Ivanov Joel Abramowitz Lutz Birnbaumer Mary Beth Humphrey Leonidas Tsiokas 《The Journal of biological chemistry》2013,288(31):22219-22232
Ca2+ signaling is essential for bone homeostasis and skeletal development. Here, we show that the transient receptor potential canonical 1 (TRPC1) channel and the inhibitor of MyoD family, I-mfa, function antagonistically in the regulation of osteoclastogenesis. I-mfa null mice have an osteopenic phenotype characterized by increased osteoclast numbers and surface, which are normalized in mice lacking both Trpc1 and I-mfa. In vitro differentiation of pre-osteoclasts derived from I-mfa-deficient mice leads to an increased number of mature osteoclasts and higher bone resorption per osteoclast. These parameters return to normal levels in osteoclasts derived from double mutant mice. Consistently, whole cell currents activated in response to the depletion of intracellular Ca2+ stores are larger in pre-osteoclasts derived from I-mfa knock-out mice compared with currents in wild type mice and normalized in cells derived from double mutant mice, suggesting a cell-autonomous effect of I-mfa on TRPC1 in these cells. A new splice variant of TRPC1 (TRPC1ϵ) was identified in early pre-osteoclasts. Heterologous expression of TRPC1ϵ in HEK293 cells revealed that it is unique among all known TRPC1 isoforms in its ability to amplify the activity of the Ca2+ release-activated Ca2+ (CRAC) channel, mediating store-operated currents. TRPC1ϵ physically interacts with Orai1, the pore-forming subunit of the CRAC channel, and I-mfa is recruited to the TRPC1ϵ-Orai1 complex through TRPC1ϵ suppressing CRAC channel activity. We propose that the positive and negative modulation of the CRAC channel by TRPC1ϵ and I-mfa, respectively, fine-tunes the dynamic range of the CRAC channel regulating osteoclastogenesis. 相似文献
15.
Anton Skopin Alexey Shalygin Vladimir Vigont Olga ZiminaLyubov Glushankova Galina N. MozhayevaElena Kaznacheyeva 《Biochimie》2013
TRPC1 is a major component of store-operated calcium entry in many cell types. In our previous studies, three types of endogenous store-operated calcium channels have been described in HEK293 cells, but it remained unknown which of these channels are composed of TRPC1 proteins. Here, this issue has been addressed by performing single-channel analysis in HEK293 cells transfected with anti-TRPC1 siRNA (siTPRC1) or a TPRC1-encoding plasmid. The results show that thapsigargin-or agonist-induced calcium influx is significantly attenuated in siTRPC1-transfected HEK293 cells. TRPC1 knockdown by siRNA results in the disappearance of store-operated Imax channels, while the properties of Imin and INS channels are unaffected. In HEK293 cells with overexpressed TRPC1 protein, the unitary current–voltage relationship of exogenous TRPC1 channels is almost linear, with a slope conductance of about 17 pS. The extrapolated reversal potential of expressed TRPC1 channels is +30 mV. Therefore, the main electrophysiological and regulatory properties of expressed TRPC1 and native Imax channels are identical. Moreover, TRPC1 overexpression in HEK293 cells results in an increased number of store-operated Imax channels. All these data allow us to conclude that TRPC1 protein forms native store-operated Imax channels but is not an essential subunit for other store-operated channel types in HEK293 cells. 相似文献
16.
Sabourin J Antigny F Robin E Frieden M Raddatz E 《The Journal of biological chemistry》2012,287(32):26688-26701
Although the activation of the A(1)-subtype of the adenosine receptors (A(1)AR) is arrhythmogenic in the developing heart, little is known about the underlying downstream mechanisms. The aim of this study was to determine to what extent the transient receptor potential canonical (TRPC) channel 3, functioning as receptor-operated channel (ROC), contributes to the A(1)AR-induced conduction disturbances. Using embryonic atrial and ventricular myocytes obtained from 4-day-old chick embryos, we found that the specific activation of A(1)AR by CCPA induced sarcolemmal Ca(2+) entry. However, A(1)AR stimulation did not induce Ca(2+) release from the sarcoplasmic reticulum. Specific blockade of TRPC3 activity by Pyr3, by a dominant negative of TRPC3 construct, or inhibition of phospholipase Cs and PKCs strongly inhibited the A(1)AR-enhanced Ca(2+) entry. Ca(2+) entry through TRPC3 was activated by the 1,2-diacylglycerol (DAG) analog OAG via PKC-independent and -dependent mechanisms in atrial and ventricular myocytes, respectively. In parallel, inhibition of the atypical PKCζ by myristoylated PKCζ pseudosubstrate inhibitor significantly decreased the A(1)AR-enhanced Ca(2+) entry in both types of myocytes. Additionally, electrocardiography showed that inhibition of TRPC3 channel suppressed transient A(1)AR-induced conduction disturbances in the embryonic heart. Our data showing that A(1)AR activation subtly mediates a proarrhythmic Ca(2+) entry through TRPC3-encoded ROC by stimulating the phospholipase C/DAG/PKC cascade provide evidence for a novel pathway whereby Ca(2+) entry and cardiac function are altered. Thus, the A(1)AR-TRPC3 axis may represent a potential therapeutic target. 相似文献
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Jingjing Song Huaping Zheng Jingwen Xue Jian Liu Qian Sun Wei Yang Fang Liu Xiangyin Xiang Kai He Younan Chen Jingqiu Cheng Wei Li Jin Jin Juergen Brosius Cheng Deng 《EMBO reports》2022,23(3)
Regulatory T lymphocyte (Treg) homing reactions mediated by G protein‐coupled receptor (GPCR)–ligand interactions play a central role in maintaining intestinal immune homeostasis by restraining inappropriate immune responses in the gastrointestinal tract. However, the origin of Treg homing to the colon remains mysterious. Here, we report that the C10ORF99 peptide (also known as CPR15L and AP57), a cognate ligand of GPR15 that controls Treg homing to the colon, originates from a duplication of the flanking CDHR1 gene and is functionally paired with GPR15 in amniotes. Evolutionary analysis and experimental data indicate that the GPR15–C10ORF99 pair is functionally conserved to mediate colonic Treg homing in amniotes and their expression patterns are positively correlated with herbivore diet in the colon. With the first herbivorous diet in early amniotes, a new biological process (herbivorous diet short‐chain fatty acid‐C10ORF99/GPR15‐induced Treg homing colon immune homeostasis) emerged, and we propose an evolutionary model whereby GPR15–C10ORF99 functional pairing has initiated the first colonic Treg homing reaction in amniotes. Our findings also highlight that GPCR–ligand pairing leads to physiological adaptation during vertebrate evolution. 相似文献
18.
Lihua Luo Yanni Zhang Hongyu Chen Fengting Hu Xiaoyan Wang Zhenjie Xing Abdullkhaleg Ali Albashari Jian Xiao Yan He Qingsong Ye 《Cell proliferation》2021,54(2)
ObjectivesVarious factors could interfere the biological performance of DPSCs during post‐thawed process. Yet, little has been known about optimization of the recovery medium for DPSCs. Thus, our study aimed to explore the effects of adding recombinant bFGF on DPSCs after 3‐month cryopreservation as well as the underlying mechanisms.Materials and methodsDPSCs were extracted from impacted third molars and purified by MACS. The properties of CD146+ DPSCs (P3) were identified by CCK‐8 and flow cytometry. After cryopreservation for 3 months, recovered DPSCs (P4) were immediately supplied with a series of bFGF and analysed cellular proliferation by CCK‐8. Then, the optimal dosage of bFGF was determined to further identify apoptosis and TRPC1 channel through Western blot. The succeeding passage (P5) from bFGF pre‐treated DPSCs was cultivated in bFGF‐free culture medium, cellular proliferation and stemness were verified, and pluripotency was analysed by neurogenic, osteogenic and adipogenic differentiation.ResultsIt is found that adding 20 ng/mL bFGF in culture medium could significantly promote the proliferation of freshly thawed DPSCs (P4) through suppressing apoptosis, activating ERK pathway and up‐regulating TRPC1. Such proliferative superiority could be inherited to the succeeding passage (P5) from bFGF pre‐stimulated DPSCs, meanwhile, stemness and pluripotency have not been compromised.ConclusionsThis study illustrated a safe and feasible cell culture technique to rapidly amplify post‐thawed DPSCs with robust regenerative potency, which brightening the future of stem cells banking and tissue engineering. 相似文献
19.
Park JY Hwang EM Yarishkin O Seo JH Kim E Yoo J Yi GS Kim DG Park N Ha CM La JH Kang D Han J Oh U Hong SG 《Biochemical and biophysical research communications》2008,368(3):677-683
We identified human TRPC3 protein by yeast two-hybrid screening of a human brain cDNA library with human TRPM4b as a bait. Immunoprecipitation and confocal microscopic analyses confirmed the protein-protein interaction between TRPM4b and TRPC3, and these two TRPs were found to be highly colocalized at the plasma membrane of HEK293T cells. Overexpression of TRPM4b suppressed TRPC3-mediated whole cell currents by more than 90% compared to those in TRPC3-expressed HEK293T cells. Furthermore, HEK293T cells stably overexpressing red fluorescent protein (RFP)-TRPM4b exhibited an almost complete abolition of UTP-induced store-operated Ca2+ entry, which is known to take place via endogenous TRPC channels in HEK293T cells. This study is believed to provide the first clear evidence that TRPM4b interacts physically with TRPC3, a member of a different TRP subfamily, and regulates negatively the channel activity, in turn suppressing store-operated Ca2+ entry through the TRPC3 channel. 相似文献
20.
Jongyun Myeong Misun Kwak Chansik Hong Ju-Hong Jeon Insuk So 《The Journal of biological chemistry》2014,289(50):34990-35002
Canonical transient receptor potential (TRPC) channels are Ca2+-permeable nonselective cation channels that are activated by a wide variety of stimuli, including G protein-coupled receptors (GPCRs). The TRPC4 channel is expressed in a punctate distribution in the membrane. To identify the regulating region of the channel trafficking to the membrane, we generated deletion mutants of the TRPC4 channel. We determined that when either region that was downstream of the 20 amino acids of the N terminus or the 700–730 amino acids was deleted, the mutants were retained in the endoplasmic reticulum. By coexpression of the wild-type TRPC4 with deletion mutants, we found that the 23–29 amino acids of the N terminus regulate a membrane trafficking. Additionally, by the fluorescence resonance energy transfer (FRET) method, we found that the regions downstream of the 99 amino acid region of the N terminus and upstream of the 730 amino acid region in the C terminus produce assembly of the TRPC4 tetramers. We inferred the candidate proteins that regulate or interact with the 23–29 domain of TRPC4. 相似文献