NDLI: Functional consequences of the over-expression of TRPC6 channels in HEK cells: impact on the homeostasis of zinc

Content Provider	Royal Society of Chemistry (RSC)
Author	Degot, Sébastien Luche, Sylvie Chevallet, Mireille Harel, Amélie Bouron, Alexandre Chapuis, Violaine Boulay, Guylain Jarvis, Louis Rabilloud, Thierry
Copyright Year	2014
Abstract	The canonical transient receptor potential 6 (TRPC6) protein is a non-selective cation channel able to transport essential trace elements like iron (Fe) and zinc (Zn) through the plasma membrane. Its over-expression in HEK-293 cells causes an intracellular accumulation of Zn, indicating that it could be involved in Zn transport. This finding prompted us to better understand the role played by TRPC6 in Zn homeostasis. Experiments done using the fluorescent probe FluoZin-3 showed that HEK cells possess an intracellular pool of mobilisable Zn present in compartments sensitive to the vesicular proton pump inhibitor Baf-A, which affects endo/lysosomes. TRPC6 over-expression facilitates the basal uptake of Zn and enhances the size of the pool of Zn sensitive to Baf-A. Quantitative RT-PCR experiments showed that TRPC6 over-expression does not affect the mRNA expression of Zn transporters (ZnT-1, ZnT-5, ZnT-6, ZnT-7, ZnT-9, Zip1, Zip6, Zip7, and Zip14); however it up-regulates the mRNA expression of metallothionein-I and -II. This alters the Zn buffering capacities of the cells as illustrated by the experiments done using the Zn ionophore Na pyrithione. In addition, HEK cells over-expressing TRPC6 grow slower than their parental HEK cells. This feature can be mimicked by growing HEK cells in a culture medium supplemented with 5 μM of Zn acetate. Finally, a proteomic analysis revealed that TRPC6 up-regulates the expression of the actin-associated proteins ezrin and cofilin-1, and changes the organisation of the actin cytoskeleton without changing the cellular actin content. Altogether, these data indicate that TRPC6 is participating in the transport of Zn and influences the Zn storage and buffering capacities of the cells.
Starting Page	1269
Ending Page	1276
Page Count	8
File Format	HTM / HTML PDF
ISSN	17565901
Volume Number	6
Issue Number	7
Journal	Metallomics
DOI	10.1039/c4mt00028e
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	TRPC6 Cell membrane Homeostasis Ion Pyrithione HEK 293 cells Protein Zinc HEK Messenger RNA Zn Transient receptor potential channel Actin Cofilin Cytoskeleton Ionophore Proton-pump inhibitor Real-time polymerase chain reaction
Content Type	Text
Resource Type	Article
Subject	Chemistry Medicine Metals and Alloys Biochemistry Biomaterials Biophysics

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

ZnT-1 extrudes zinc from mammalian cells functioning as a Zn²⁺/H⁺ exchanger

Study of diacylglycerol-activated TRPC6 channels in murine cortical neurons and their roles in the transport of transition metals

Understanding metal homeostasis in primary cultured neurons. Studies using single neuron subcellular and quantitative metallomics

Efflux function, tissue-specific expression and intracellular trafficking of the Zn transporter ZnT10 indicate roles in adult Zn homeostasis

The over-expression of TRPC6 channels in HEK-293 cells favours the intracellular accumulation of zinc.

Roles of copper chaperone for superoxide dismutase 1 and metallothionein in copper homeostasis

d-Histidine and l-histidine attenuate zinc-induced neuronal death in GT1-7 cells

Molecular and genetic features of zinc transporters in physiology and pathogenesis

Heterogeneous distribution of natural zinc isotopes in mice

Functional consequences of the over-expression of TRPC6 channels in HEK cells: impact on the homeostasis of zinc

Similar Documents

ZnT-1 extrudes zinc from mammalian cells functioning as a Zn2+/H+ exchanger

Study of diacylglycerol-activated TRPC6 channels in murine cortical neurons and their roles in the transport of transition metals

Understanding metal homeostasis in primary cultured neurons. Studies using single neuron subcellular and quantitative metallomics

Efflux function, tissue-specific expression and intracellular trafficking of the Zn transporter ZnT10 indicate roles in adult Zn homeostasis

The over-expression of TRPC6 channels in HEK-293 cells favours the intracellular accumulation of zinc.

Roles of copper chaperone for superoxide dismutase 1 and metallothionein in copper homeostasis

d-Histidine and l-histidine attenuate zinc-induced neuronal death in GT1-7 cells

Molecular and genetic features of zinc transporters in physiology and pathogenesis

Heterogeneous distribution of natural zinc isotopes in mice

Functional consequences of the over-expression of TRPC6 channels in HEK cells: impact on the homeostasis of zinc

ZnT-1 extrudes zinc from mammalian cells functioning as a Zn²⁺/H⁺ exchanger