Plasma membrane curvature regulates the formation of contacts with the endoplasmic reticulum.

Autor: Yang Y; Department of Chemistry, Stanford University, Stanford, CA, USA.; Wu Tsai Neurosciences Institute and ChEM-H Institute, Stanford University, Stanford, CA, USA., Valencia LA; Department of Chemistry, Stanford University, Stanford, CA, USA.; Wu Tsai Neurosciences Institute and ChEM-H Institute, Stanford University, Stanford, CA, USA., Lu CH; Department of Chemistry, Stanford University, Stanford, CA, USA.; Wu Tsai Neurosciences Institute and ChEM-H Institute, Stanford University, Stanford, CA, USA., Nakamoto ML; Department of Chemistry, Stanford University, Stanford, CA, USA.; Wu Tsai Neurosciences Institute and ChEM-H Institute, Stanford University, Stanford, CA, USA., Tsai CT; Department of Chemistry, Stanford University, Stanford, CA, USA.; Wu Tsai Neurosciences Institute and ChEM-H Institute, Stanford University, Stanford, CA, USA., Liu C; Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA.; Departments of Physiology and Medicine, Medical College of Wisconsin, Milwaukee, WI, USA., Yang H; Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA.; Department of Biomedical Engineering, University of North Texas, Denton, TX, USA., Zhang W; Department of Chemistry, Stanford University, Stanford, CA, USA.; Wu Tsai Neurosciences Institute and ChEM-H Institute, Stanford University, Stanford, CA, USA., Jahed Z; Department of Chemistry, Stanford University, Stanford, CA, USA.; Department of Chemical and Nano Engineering, University of California, San Diego, San Diego, CA, USA., Lee WR; Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX, USA., Santoro F; Tissue Electronics, Istituto Italiano di Tecnologia, Naples, Italy.; Faculty of Electrical Engineering and Information Technology, RWTH Aachen University, Aachen, Germany.; Institute of Biological Information Processing-Bioelectronics (IBI-3), Forschungszentrum, Jülich, Germany., Liou J; Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX, USA., Wu JC; Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA.; Department of Medicine, Division of Cardiology, Stanford University, Stanford, CA, USA.; Department of Radiology, Stanford University, Stanford, CA, USA., Cui B; Department of Chemistry, Stanford University, Stanford, CA, USA. bcui@stanford.edu.; Wu Tsai Neurosciences Institute and ChEM-H Institute, Stanford University, Stanford, CA, USA. bcui@stanford.edu.
Jazyk: angličtina
Zdroj: Nature cell biology [Nat Cell Biol] 2024 Nov; Vol. 26 (11), pp. 1878-1891. Date of Electronic Publication: 2024 Sep 17.
DOI: 10.1038/s41556-024-01511-x
Abstrakt: Contact sites between the endoplasmic reticulum (ER) and plasma membrane (PM) play a crucial role in governing calcium regulation and lipid homeostasis. Despite their significance, the factors regulating their spatial distribution on the PM remain elusive. Inspired by observations in cardiomyocytes, where ER-PM contact sites concentrate on tubular PM invaginations known as transverse tubules, we hypothesize that PM curvature plays a role in ER-PM contact formation. Through precise control of PM invaginations, we show that PM curvatures locally induce the formation of ER-PM contacts in cardiomyocytes. Intriguingly, the junctophilin family of ER-PM tethering proteins, specifically expressed in excitable cells, is the key player in this process, whereas the ubiquitously expressed extended synaptotagmin-2 does not show a preference for PM curvature. At the mechanistic level, we find that the low-complexity region (LCR) and membrane occupation and recognition nexus (MORN) motifs of junctophilins can bind independently to the PM, but both the LCR and MORN motifs are required for targeting PM curvatures. By examining the junctophilin interactome, we identify a family of curvature-sensing proteins-Eps15 homology domain-containing proteins-that interact with the MORN_LCR motifs and facilitate the preferential tethering of junctophilins to curved PM. These findings highlight the pivotal role of PM curvature in the formation of ER-PM contacts in cardiomyocytes and unveil a mechanism for the spatial regulation of ER-PM contacts through PM curvature modulation.
Competing Interests: Competing interests The authors declare no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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