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Fast endocytic recycling determines TRPC1-STIM1 clustering in ER-PM junctions and plasma membrane function of the channel.
Biochim Biophys Acta. 2015 Oct; 1853(10 Pt A):2709-21.BB

Abstract

Stromal interaction molecule 1 (STIM1) senses depletion of ER-Ca2+ store and clusters in ER-PM junctions where it associates with and gates Ca2+ influx channels, Orai1 and TRPC1. Clustering of TRPC1 with STIM1 and Orai1 in these junctions is critical since Orai1-mediated Ca2+ entry triggers surface expression of TRPC1 while STIM1 gates the channel. Thus, plasma membrane function of TRPC1 depends on the delivery of the channel to the sites where STIM1 puncta are formed. This study examines intracellular trafficking mechanism(s) that determine plasma membrane expression and function of TRPC1 in cells where Orai1 and TRPC1 are endogenously expressed and contribute to Ca2+ entry. We report that TRPC1 is internalized by Arf6-dependent pathway, sorted to Rab5-containing early endosomes, and trafficked to ER-PM junctions by Rab4-dependent fast recycling. Overexpression of Arf6, or Rab5, but not the respective dominant negative mutants, induced retention of TRPC1 in early endosomes and suppressed TRPC1 function. Notably, cells expressing Arf6 or Rab5 displayed an inwardly rectifying ICRAC current that is mediated by Orai1 instead of TRPC1-associated ISOC, demonstrating that Orai1 function was not altered. Importantly, expression of Rab4, but not STIM1, with Rab5 rescued surface expression and function of TRPC1, restoring generation of ISOC. Together, these data demonstrate that trafficking via fast recycling endosomes determines TRPC1-STIM1 clustering within ER-PM junctions following ER-Ca2+ store depletion which is critical for the surface expression and function of the channel. Ca2+ influx mediated by TRPC1 modifies Ca2+-dependent physiological response of cells.

Authors+Show Affiliations

Secretory Physiology Section, Molecular Physiology and Therapeutics Branch, NIDCR, NIH, MD 20892, USA.Secretory Physiology Section, Molecular Physiology and Therapeutics Branch, NIDCR, NIH, MD 20892, USA.Secretory Physiology Section, Molecular Physiology and Therapeutics Branch, NIDCR, NIH, MD 20892, USA.Secretory Physiology Section, Molecular Physiology and Therapeutics Branch, NIDCR, NIH, MD 20892, USA. Electronic address: indu.ambudkar@nih.gov.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

26232624

Citation

de Souza, Lorena Brito, et al. "Fast Endocytic Recycling Determines TRPC1-STIM1 Clustering in ER-PM Junctions and Plasma Membrane Function of the Channel." Biochimica Et Biophysica Acta, vol. 1853, no. 10 Pt A, 2015, pp. 2709-21.
de Souza LB, Ong HL, Liu X, et al. Fast endocytic recycling determines TRPC1-STIM1 clustering in ER-PM junctions and plasma membrane function of the channel. Biochim Biophys Acta. 2015;1853(10 Pt A):2709-21.
de Souza, L. B., Ong, H. L., Liu, X., & Ambudkar, I. S. (2015). Fast endocytic recycling determines TRPC1-STIM1 clustering in ER-PM junctions and plasma membrane function of the channel. Biochimica Et Biophysica Acta, 1853(10 Pt A), 2709-21. https://doi.org/10.1016/j.bbamcr.2015.07.019
de Souza LB, et al. Fast Endocytic Recycling Determines TRPC1-STIM1 Clustering in ER-PM Junctions and Plasma Membrane Function of the Channel. Biochim Biophys Acta. 2015;1853(10 Pt A):2709-21. PubMed PMID: 26232624.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fast endocytic recycling determines TRPC1-STIM1 clustering in ER-PM junctions and plasma membrane function of the channel. AU - de Souza,Lorena Brito, AU - Ong,Hwei Ling, AU - Liu,Xibao, AU - Ambudkar,Indu S, Y1 - 2015/07/30/ PY - 2015/05/22/received PY - 2015/07/24/revised PY - 2015/07/28/accepted PY - 2015/8/2/entrez PY - 2015/8/2/pubmed PY - 2015/12/15/medline KW - Endocytic recycling KW - Orai1 KW - STIM1 KW - Store-operated calcium entry KW - Surface expression KW - TRPC1 SP - 2709 EP - 21 JF - Biochimica et biophysica acta JO - Biochim. Biophys. Acta VL - 1853 IS - 10 Pt A N2 - Stromal interaction molecule 1 (STIM1) senses depletion of ER-Ca2+ store and clusters in ER-PM junctions where it associates with and gates Ca2+ influx channels, Orai1 and TRPC1. Clustering of TRPC1 with STIM1 and Orai1 in these junctions is critical since Orai1-mediated Ca2+ entry triggers surface expression of TRPC1 while STIM1 gates the channel. Thus, plasma membrane function of TRPC1 depends on the delivery of the channel to the sites where STIM1 puncta are formed. This study examines intracellular trafficking mechanism(s) that determine plasma membrane expression and function of TRPC1 in cells where Orai1 and TRPC1 are endogenously expressed and contribute to Ca2+ entry. We report that TRPC1 is internalized by Arf6-dependent pathway, sorted to Rab5-containing early endosomes, and trafficked to ER-PM junctions by Rab4-dependent fast recycling. Overexpression of Arf6, or Rab5, but not the respective dominant negative mutants, induced retention of TRPC1 in early endosomes and suppressed TRPC1 function. Notably, cells expressing Arf6 or Rab5 displayed an inwardly rectifying ICRAC current that is mediated by Orai1 instead of TRPC1-associated ISOC, demonstrating that Orai1 function was not altered. Importantly, expression of Rab4, but not STIM1, with Rab5 rescued surface expression and function of TRPC1, restoring generation of ISOC. Together, these data demonstrate that trafficking via fast recycling endosomes determines TRPC1-STIM1 clustering within ER-PM junctions following ER-Ca2+ store depletion which is critical for the surface expression and function of the channel. Ca2+ influx mediated by TRPC1 modifies Ca2+-dependent physiological response of cells. SN - 0006-3002 UR - https://www.unboundmedicine.com/medline/citation/26232624/Fast_endocytic_recycling_determines_TRPC1_STIM1_clustering_in_ER_PM_junctions_and_plasma_membrane_function_of_the_channel_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0167-4889(15)00256-6 DB - PRIME DP - Unbound Medicine ER -