Dynamic formation of ER-PM junctions presents a lipid phosphatase to regulate phosphoinositides

Endoplasmic reticulum-plasma membrane (ER-PM) contact sites play an integral role in cellular processes such as excitation-contraction coupling and store-operated calcium entry (SOCE). Another ER-PM assembly is one tethered by the extended synaptotagmins (E-Syt). We have discovered that at steady st...

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Veröffentlicht in:The Journal of cell biology Jg. 213; H. 1; S. 33
Hauptverfasser: Dickson, Eamonn J, Jensen, Jill B, Vivas, Oscar, Kruse, Martin, Traynor-Kaplan, Alexis E, Hille, Bertil
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 11.04.2016
Schlagworte:
Animals
Calcium - metabolism
Cell Line
Cell Membrane - metabolism
Endoplasmic Reticulum - metabolism
Humans
Male
Membrane Proteins - metabolism
Phosphatidylinositol 4,5-Diphosphate - metabolism
Phosphatidylinositol Phosphates - metabolism
Phosphatidylinositols - metabolism
Phosphoric Monoester Hydrolases - metabolism
Rats
Rats, Sprague-Dawley
Synaptotagmins - metabolism
ISSN:1540-8140, 1540-8140
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Zusammenfassung:Endoplasmic reticulum-plasma membrane (ER-PM) contact sites play an integral role in cellular processes such as excitation-contraction coupling and store-operated calcium entry (SOCE). Another ER-PM assembly is one tethered by the extended synaptotagmins (E-Syt). We have discovered that at steady state, E-Syt2 positions the ER and Sac1, an integral ER membrane lipid phosphatase, in discrete ER-PM junctions. Here, Sac1 participates in phosphoinositide homeostasis by limiting PM phosphatidylinositol 4-phosphate (PI(4)P), the precursor of PI(4,5)P2 Activation of G protein-coupled receptors that deplete PM PI(4,5)P2disrupts E-Syt2-mediated ER-PM junctions, reducing Sac1's access to the PM and permitting PM PI(4)P and PI(4,5)P2to recover. Conversely, depletion of ER luminal calcium and subsequent activation of SOCE increases the amount of Sac1 in contact with the PM, depleting PM PI(4)P. Thus, the dynamic presence of Sac1 at ER-PM contact sites allows it to act as a cellular sensor and controller of PM phosphoinositides, thereby influencing many PM processes.
Bibliographie:ObjectType-Article-1
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ISSN:1540-8140
1540-8140
DOI:10.1083/jcb.201508106