A central role of the endoplasmic reticulum in the cell emerges from its functional contact sites with multiple organelles

Abstract

Early eukaryotic cells emerged from the compartmentalization of metabolic processes into specific organelles through the development of an endomembrane system (ES), a precursor of the endoplasmic reticulum (ER), which was essential for their survival. Recently, substantial evidence emerged on how organelles communicate among themselves and with the plasma membrane (PM) through contact sites (CSs). From these studies, the ER—the largest single structure in eukaryotic cells—emerges as a central player communicating with all organelles to coordinate cell functions and respond to external stimuli to maintain cellular homeostasis. Herein we review the functional insights into the ER–CSs with other organelles in a physiological perspective. We hypothesize that, in addition to the primitive role by the ES in the appearance of proto-eukaryotes, its successor—the ER—emerges as the key coordinator of inter-organelle/PM communication. The ER thus appears to be the ‘maestro’ driving eukaryotic cell evolution by incorporating new functions/organelles, while remaining the real coordinator overarching cellular functions and orchestrating them with the external milieu.

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Abbreviations

AD:

Alzheimer's disease

ALS:

Amyotrophic lateral sclerosis

AM:

Arbuscular mycorrhizae

CHL:

Chloroplast

EE(s):

Early endosome(s)

ER:

Endoplasmic reticulum

ERAD:

ER-associated (protein) degradation

ERGIC:

ER-Golgi intermediate compartment

ERMES:

ER-mitochondrial tethering complex

FTD:

Fronto-temporal dementia

MAM:

Mitochondria-associated ER membranes

ES:

Endomembrane system

GFP:

Green fluorescent protein

IM:

Isolation membrane

LD(s):

Lipid droplet(s)

LE(s):

Late endosome(s)

LTP(s):

Lipid-transfer protein(s)

MCS(s):

Membrane contact site(s)

MITO:

Mitochondria

MT (s):

Microtubule(s)

PD:

Parkinson’s disease

PH:

Pleckstrin homology (domain)

PLAM(s):

Plastid-associated membranes

PLD:

Plasmodesmata

PM:

Plasma membrane

PMCS(s):

Plasma membrane contact site(s)

PMP(s):

Peroxisomal membrane proteins(s)

PPA:

Pre-penetration apparatus

PV(s):

Parasitophorous vacuole(s)

PBs:

Processing bodies

RER:

Rough ER

SER:

Smooth ER

SE(s):

Steryl ester(s)

SOCE:

Store-operated Ca2+ entry

STIM:

Stromal interaction molecule

TEM:

Transmission electron microscopy

TG:

Triacylglycerol

TPC(s):

Two-pore channel(s)

TRP(s):

Transient receptor potential channel(s)

VAP(s):

Vesicle-associated membrane protein-associated protein(s

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Acknowledgements

C. Almeida was the recipient of a fellowship from Fundação para a Ciência e Tecnologia, FCT, Portugal (fellowship SFRH/BPD/77720/2011). Work in MD Amaral’s lab is supported by UID/MULTI/04046/2019 centre grant (to BioISI) and research grants from FCT/MCTES Portugal (PTDC/BIM-MEC/2131/2014) “DiffTarget”, FCT/02/SAICT/2017/28800) “iDrugCF, “HIT-CF” and CF Trust UK (SRC 013).

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Almeida, C., Amaral, M.D. A central role of the endoplasmic reticulum in the cell emerges from its functional contact sites with multiple organelles. Cell. Mol. Life Sci. 77, 4729–4745 (2020). https://doi.org/10.1007/s00018-020-03523-w

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Keywords

  • Organellar functions
  • Organelle interactions
  • Organelle disorders
  • Endosymbiosis
  • Mitochondria
  • Lysosomes