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The polybasic lysine-rich domain of plasma membrane-resident STIM1 is essential for the modulation of store-operated divalent cation entry by extracellular calcium.
Cell Signal. 2013 May; 25(5):1328-37.CS

Abstract

STIM1 acts as an endoplasmic reticulum Ca(2+) sensor that communicates the filling state of the intracellular stores to the store-operated channels. In addition, STIM1 is expressed in the plasma membrane, with the Ca(2+) binding EF-hand motif facing the extracellular medium; however, its role sensing extracellular Ca(2+) concentrations in store-operated Ca(2+) entry (SOCE), as well as the underlying mechanism remains unclear. Here we report that divalent cation entry stimulated by thapsigargin (TG) is attenuated by extracellular Ca(2+) in a concentration-dependent manner. Expression of the Ca(2+)-binding defective STIM1(D76A) mutant did not alter the surface expression of STIM1 but abolishes the regulation of divalent cation entry by extracellular Ca(2+). Orai1 and TRPC1 have been shown to play a major role in SOCE. Expression of the STIM1(D76A) mutant did not alter Orai1 phosphoserine content. TRPC1 silencing significantly attenuated TG-induced Mn(2+) entry. Expression of the STIM1(K684,685E) mutant impaired the association of plasma membrane STIM1 with TRPC1, as well as the regulation of TG-induced divalent cation entry by extracellular Ca(2+), which suggests that TRPC1 might be involved in the regulation of divalent cation entry by extracellular Ca(2+) mediated by plasma membrane-resident STIM1. Expression of the STIM1(D76A) or STIM1(K684,685E) mutants reduced store-operated divalent cation entry and resulted in loss of dependence on the extracellular Ca(2+) concentration, providing evidence for a functional role of plasma membrane-resident STIM1 in the regulation of store-operated divalent cation entry, which at least involves the EF-hand motif and the C-terminal polybasic lysine-rich domain.

Authors+Show Affiliations

Institute of Biophysics, University of Linz, A-4040 Linz, Austria.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23395841

Citation

Jardin, Isaac, et al. "The Polybasic Lysine-rich Domain of Plasma Membrane-resident STIM1 Is Essential for the Modulation of Store-operated Divalent Cation Entry By Extracellular Calcium." Cellular Signalling, vol. 25, no. 5, 2013, pp. 1328-37.
Jardin I, Dionisio N, Frischauf I, et al. The polybasic lysine-rich domain of plasma membrane-resident STIM1 is essential for the modulation of store-operated divalent cation entry by extracellular calcium. Cell Signal. 2013;25(5):1328-37.
Jardin, I., Dionisio, N., Frischauf, I., Berna-Erro, A., Woodard, G. E., López, J. J., Salido, G. M., & Rosado, J. A. (2013). The polybasic lysine-rich domain of plasma membrane-resident STIM1 is essential for the modulation of store-operated divalent cation entry by extracellular calcium. Cellular Signalling, 25(5), 1328-37. https://doi.org/10.1016/j.cellsig.2013.01.025
Jardin I, et al. The Polybasic Lysine-rich Domain of Plasma Membrane-resident STIM1 Is Essential for the Modulation of Store-operated Divalent Cation Entry By Extracellular Calcium. Cell Signal. 2013;25(5):1328-37. PubMed PMID: 23395841.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The polybasic lysine-rich domain of plasma membrane-resident STIM1 is essential for the modulation of store-operated divalent cation entry by extracellular calcium. AU - Jardin,Isaac, AU - Dionisio,Natalia, AU - Frischauf,Irene, AU - Berna-Erro,Alejandro, AU - Woodard,Geoffrey E, AU - López,José J, AU - Salido,Ginés M, AU - Rosado,Juan A, Y1 - 2013/02/08/ PY - 2012/11/13/received PY - 2013/01/09/revised PY - 2013/01/23/accepted PY - 2013/2/12/entrez PY - 2013/2/12/pubmed PY - 2013/10/19/medline SP - 1328 EP - 37 JF - Cellular signalling JO - Cell Signal VL - 25 IS - 5 N2 - STIM1 acts as an endoplasmic reticulum Ca(2+) sensor that communicates the filling state of the intracellular stores to the store-operated channels. In addition, STIM1 is expressed in the plasma membrane, with the Ca(2+) binding EF-hand motif facing the extracellular medium; however, its role sensing extracellular Ca(2+) concentrations in store-operated Ca(2+) entry (SOCE), as well as the underlying mechanism remains unclear. Here we report that divalent cation entry stimulated by thapsigargin (TG) is attenuated by extracellular Ca(2+) in a concentration-dependent manner. Expression of the Ca(2+)-binding defective STIM1(D76A) mutant did not alter the surface expression of STIM1 but abolishes the regulation of divalent cation entry by extracellular Ca(2+). Orai1 and TRPC1 have been shown to play a major role in SOCE. Expression of the STIM1(D76A) mutant did not alter Orai1 phosphoserine content. TRPC1 silencing significantly attenuated TG-induced Mn(2+) entry. Expression of the STIM1(K684,685E) mutant impaired the association of plasma membrane STIM1 with TRPC1, as well as the regulation of TG-induced divalent cation entry by extracellular Ca(2+), which suggests that TRPC1 might be involved in the regulation of divalent cation entry by extracellular Ca(2+) mediated by plasma membrane-resident STIM1. Expression of the STIM1(D76A) or STIM1(K684,685E) mutants reduced store-operated divalent cation entry and resulted in loss of dependence on the extracellular Ca(2+) concentration, providing evidence for a functional role of plasma membrane-resident STIM1 in the regulation of store-operated divalent cation entry, which at least involves the EF-hand motif and the C-terminal polybasic lysine-rich domain. SN - 1873-3913 UR - https://www.unboundmedicine.com/medline/citation/23395841/The_polybasic_lysine_rich_domain_of_plasma_membrane_resident_STIM1_is_essential_for_the_modulation_of_store_operated_divalent_cation_entry_by_extracellular_calcium_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0898-6568(13)00036-3 DB - PRIME DP - Unbound Medicine ER -