GRAM domain proteins specialize functionally distinct ER-PM contact sites in human cells

© 2018, Besprozvannaya et al..

Endoplasmic reticulum (ER) membrane contact sites (MCSs) are crucial regulatory hubs in cells, playing roles in signaling, organelle dynamics, and ion and lipid homeostasis. Previous work demonstrated that the highly conserved yeast Ltc/Lam sterol transporters localize and function at ER MCSs. Our analysis of the human family members, GRAMD1a and GRAMD2a, demonstrates that they are ER-PM MCS proteins, which mark separate regions of the plasma membrane (PM) and perform distinct functions in vivo. GRAMD2a, but not GRAMD1a, co-localizes with the E-Syt2/3 tethers at ER-PM contacts in a PIP lipid-dependent manner and pre-marks the subset of PI(4,5)P2-enriched ER-PM MCSs utilized for STIM1 recruitment. Data from an analysis of cells lacking GRAMD2a suggest that it is an organizer of ER-PM MCSs with pleiotropic functions including calcium homeostasis. Thus, our data demonstrate the existence of multiple ER-PM domains in human cells that are functionally specialized by GRAM-domain containing proteins.

Errataetall:

CommentIn: Cell Calcium. 2018 Jul;73:70-71. - PMID 29684786

Medienart:

E-Artikel

Erscheinungsjahr:

2018

Erschienen:

2018

Enthalten in:

Zur Gesamtaufnahme - volume:7

Enthalten in:

eLife - 7(2018) vom: 22. Feb.

Sprache:

Englisch

Beteiligte Personen:

Besprozvannaya, Marina [VerfasserIn]
Dickson, Eamonn [VerfasserIn]
Li, Hao [VerfasserIn]
Ginburg, Kenneth S [VerfasserIn]
Bers, Donald M [VerfasserIn]
Auwerx, Johan [VerfasserIn]
Nunnari, Jodi [VerfasserIn]

Links:

Volltext

Themen:

134193-27-4
Calcium
Cell biology
Cortical ER
ER-PM contact sites
ESYT2 protein, human
ESYT3 protein, human
GRAMD proteins
GRAMD1A protein, human
GRAMD2A protein, human
Human
Journal Article
Membrane Proteins
Membrane contact site
Neoplasm Proteins
PIP lipids
Phosphatidylinositol Phosphates
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
STIM1 protein, human
SY7Q814VUP
Store operated calcium entry
Stromal Interaction Molecule 1
Synaptotagmins

Anmerkungen:

Date Completed 16.07.2019

Date Revised 25.10.2019

published: Electronic

CommentIn: Cell Calcium. 2018 Jul;73:70-71. - PMID 29684786

Citation Status MEDLINE

doi:

10.7554/eLife.31019

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM28128038X