Dataset Information

TMEM41B is an endoplasmic reticulum Ca2+ release channel maintaining naive T cell quiescence and responsiveness

ABSTRACT: In mammalian cells, endoplasmic reticulum (ER) passively releases Ca2+ under steady state, but channels involved remain elusive. Here, we report that TMEM41B, an ER-resident membrane protein critical for autophagy, lipid metabolism, and viral infection, functions as an ER Ca2+ release channel. Biochemically, purified recombinant TMEM41B forms a concentration-dependent Ca2+ channel in single-channel electrophysiology assays. Cellularly, TMEM41B deficiency causes ER Ca2+ overload, while overexpression of TMEM41B depletes ER Ca2+. Immunologically, ER Ca2+ overload leads to upregulation of IL-2 and IL-7 receptors in naive T cells, which in turn increases basal signaling of JAK-STAT, AKT-mTOR, and MAPK pathways. This dysregulation drives TMEM41B-deficient naive T cells into a metabolically activated yet immunologically naive state. ER Ca2+ overload also downregulates CD5, lowering the activation threshold of TMEM41B-deficient T cells and leading to heightened T cell responses during infections. In summary, we identify TMEM41B as a concentration-dependent ER Ca2+ release channel, revealing an unexpected role of ER Ca2+ in naive T cell quiescence and responsiveness.

ORGANISM(S): Mus musculus

PROVIDER: GSE285373 | GEO | 2025/03/01

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:This a model from the article: A dynamic model of the cardiac ventricular action potential. I. Simulations of ionic currents and concentration changes. Luo CH, Rudy Y. Circ Res 1994 Jun;74(6):1071-96 7514509 , Abstract: A mathematical model of the cardiac ventricular action potential is presented. In our previous work, the membrane Na+ current and K+ currents were formulated. The present article focuses on processes that regulate intracellular Ca2+ and depend on its concentration. The model presented here for the mammalian ventricular action potential is based mostly on the guinea pig ventricular cell. However, it provides the framework for modeling other types of ventricular cells with appropriate modifications made to account for species differences. The following processes are formulated: Ca2+ current through the L-type channel (ICa), the Na(+)-Ca2+ exchanger, Ca2+ release and uptake by the sarcoplasmic reticulum (SR), buffering of Ca2+ in the SR and in the myoplasm, a Ca2+ pump in the sarcolemma, the Na(+)-K+ pump, and a nonspecific Ca(2+)-activated membrane current. Activation of ICa is an order of magnitude faster than in previous models. Inactivation of ICa depends on both the membrane voltage and [Ca2+]i. SR is divided into two subcompartments, a network SR (NSR) and a junctional SR (JSR). Functionally, Ca2+ enters the NSR and translocates to the JSR following a monoexponential function. Release of Ca2+ occurs at JSR and can be triggered by two different mechanisms, Ca(2+)-induced Ca2+ release and spontaneous release. The model provides the basis for the study of arrhythmogenic activity of the single myocyte including afterdepolarizations and triggered activity. It can simulate cellular responses under different degrees of Ca2+ overload. Such simulations are presented in our accompanying article in this issue of Circulation Research. This model was taken from the CellML repository and automatically converted to SBML. The original model was: Luo CH, Rudy Y. (1994) - version02 This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information. In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not.. To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

Project description:Wang2007 - ATP induced intracellular Calicum Oscillation The model simulate the ATP-induced intracellular Ca2+ oscillations and the quantitative effect of ATP concentration on the oscillation characteristics such as the duration, peak concentration of intracellular Ca2+ and average interval. This model is described in the article: A quantitative kinetic model for ATP-induced intracellular Ca2+ oscillations. Wang J, Huang X, Huang W. J. Theor. Biol. 2007 Apr; 245(3): 510-519 Abstract: A quantitative kinetic model is proposed to simulate the ATP-induced intracellular Ca(2+) oscillations. The quantitative effect of ATP concentration upon the oscillations was successfully simulated. Our simulation results support previous experimental explanations that the Ca(2+) oscillations are mainly due to interaction of Ca(2+) release from the endoplasmic reticulum (ER) and the ATP-dependent Ca(2+) pump back into the ER, and the oscillations are prolonged by extracellular Ca(2+) entry that maintains the constant Ca(2+) supplies to its intracellular stores. The model is also able to simulate the sudden disappearance phenomenon of the Ca(2+) oscillations observed in some cell types by taking into account of the biphasic characteristic of the Ca(2+) release from the endoplasmic reticulum (ER). Moreover, the model simulation results for the Ca(2+) oscillations characteristics such as duration, peak [Ca(2+)](cyt), and average interval, etc., lead to prediction of some possible factors responsible for the variations of Ca(2+) oscillations in different types of cells. This model is hosted on BioModels Database and identified by: BIOMD0000000145. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Dataset Information

TMEM41B is an endoplasmic reticulum Ca2+ release channel maintaining naive T cell quiescence and responsiveness

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets