Premium
Triggered Ca 2+ influx is required for extended synaptotagmin 1‐induced ER ‐plasma membrane tethering
Author(s) -
IdevallHagren Olof,
Lü Alice,
Xie Beichen,
De Camilli Pietro
Publication year - 2015
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201591565
Subject(s) - tethering , biology , synaptotagmin 1 , microbiology and biotechnology , membrane , biophysics , genetics , vesicle , synaptic vesicle
The extended synaptotagmins (E‐Syts) are ER proteins that act as Ca 2+ ‐regulated tethers between the ER and the plasma membrane ( PM ) and have a putative role in lipid transport between the two membranes. Ca 2+ regulation of their tethering function, as well as the interplay of their different domains in such function, remains poorly understood. By exposing semi‐intact cells to buffers of variable Ca 2+ concentrations, we found that binding of E‐Syt1 to the PI (4,5)P 2 ‐rich PM critically requires its C2C and C2E domains and that the EC 50 of such binding is in the low micromolar Ca 2+ range. Accordingly, E‐Syt1 accumulation at ER ‐ PM contact sites occurred only upon experimental manipulations known to achieve these levels of Ca 2+ via its influx from the extracellular medium, such as store‐operated Ca 2+ entry in fibroblasts and membrane depolarization in β‐cells. We also show that in spite of their very different physiological functions, membrane tethering by E‐Syt1 ( ER to PM ) and by synaptotagmin (secretory vesicles to PM ) undergo a similar regulation by plasma membrane lipids and cytosolic Ca 2+ .