The molecular basis of tricalbin-mediated membrane contact site organization in cells
Publisher DOI
PubMed ID
41948883
Abstract
Membrane contact sites facilitate molecular exchanges through physical interactions between organelles, connected by specific protein tethers. Among these tethers are the tricalbins, which mediate contacts between endoplasmic reticulum (ER) and plasma membrane in yeast. Tricalbins are integral to the ER, have a cytosolic lipid binding domain and bind the plasma membrane through C2 domains. Here, we combine fluorescence recovery after photobleaching with correlative light and 3D electron microscopy to dissect how tricalbins control their localization, dynamic distribution and contact site organization. We find that heteromerization via lipid binding domains is a prerequisite for tricalbin accumulation at contact sites, membrane curvature sensing and restrained mobility in the ER. By altering tricalbin protein domains, we show that intermembrane distances and intrinsically disordered regions interdependently control distribution and dynamics of contact site tethers. Our study reveals principles of contact site architecture that are fine-tuned by tricalbin domain organization.
Date Issued
2026
Publication Type
Article
Subjects
Correlative light and electron microscopy
•
FRAP
•
Live imaging
•
Membrane contact sites
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Tricalbins
•
Yeast
Language(s)
en
Author(s)
Boinet, Anne-Laure | |
Picco, Andrea | |
Ross-Kaschitza, Daniela | |
Kaksonen, Marko |
Journal
Journal of Cell Science
Publisher
The Company of Biologists
ISSN
0021-9533
1477-9137
Access(Rights)
open.access