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IP3 Receptor Properties and Function at Membrane Contact Sites

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Membrane Dynamics and Calcium Signaling

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 981))

Abstract

The inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) is a ubiquitously expressed Ca2+-release channel localized in the endoplasmic reticulum (ER). The intracellular Ca2+ signals originating from the activation of the IP3R regulate multiple cellular processes including the control of cell death versus cell survival via their action on apoptosis and autophagy. The exact role of the IP3Rs in these two processes does not only depend on their activity, which is modulated by the cytosolic composition (Ca2+, ATP, redox status, …) and by various types of regulatory proteins, including kinases and phosphatases as well as by a number of oncogenes and tumor suppressors, but also on their intracellular localization, especially at the ER-mitochondrial and ER-lysosomal interfaces. At these interfaces, Ca2+ microdomains are formed, in which the Ca2+ concentration is finely regulated by the different ER, mitochondrial and lysosomal Ca2+-transport systems and also depends on the functional and structural interactions existing between them. In this review, we therefore discuss the most recent insights in the role of Ca2+ signaling in general, and of the IP3R in particular, in the control of basal mitochondrial bioenergetics, apoptosis, and autophagy at the level of inter-organellar contact sites.

Gemma Roest and Rita M. La Rovere are Joint first authors.

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Abbreviations

ALS:

Amyotrophic lateral sclerosis

AMPK:

AMP-activated kinase

ATG:

Autophagy-related

BIRD-2:

Bcl-2/IP3R disruptor-2 peptide

CICR:

Ca2+-induced Ca2+ release

CREB:

cAMP response element-binding protein

DT40 TKO:

DT40 IP3R triple knock-out

ER:

Endoplasmic reticulum

Fis1:

Fission 1 homologue

GRP75:

Glucose-regulated protein 75

GRP78/BiP:

Glucose-regulated protein 78

GSK3β:

Glycogen synthase kinase-3β

IMM:

Inner mitochondrial membrane

IBC:

IP3-binding core

IP3:

Inositol 1,4,5-trisphosphate

IP3R:

IP3 receptor

LC3:

Microtubule-associated protein light chain 3

LRRK2:

Leucine-rich repeat kinase 2

MAM:

Mitochondria-associated ER membrane

MCU:

Mitochondrial Ca2+ uniporter

Mfn:

Mitofusin

mPTP:

Mitochondrial permeabilization transition pore

mTORC1:

Mechanistic target of rapamycin complex 1

OMM:

Outer mitochondrial membrane

NAADP:

Nicotinic acid adenine dinucleotide phosphate

PACS-2:

Phosphofurin acidic cluster sorting protein 2

PERK:

Protein kinase RNA-like ER kinase

PIP3:

Phosphatidylinositol 3,4,5-trisphosphate

PKB/Akt:

Protein kinase B

PML:

Promyelocytic leukemia

PTEN:

Phosphatase and tensin homolog

PTPIP51:

Protein tyrosine phosphatase-interacting protein-51

ROS:

Reactive oxygen species

RyR:

Ryanodine receptor

SERCA:

Sarco-/endoplasmic reticulum Ca2+ ATPase

TCA:

Tricarboxylic acid

TFEB:

Transcription factor EB

TMX:

Thioredoxin-like transmembrane protein

TPC:

Two-pore channel

TRPML:

Transient receptor potential mucolipin

ULK1/2:

Atg1/Unc-51-like kinase 1/2

UPR:

Unfolded protein response

VAPB:

Vesicle-associated protein B

VDAC:

Voltage-dependent anion channel

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Acknowledgements

GR is recipient of a Ph.D. fellowship of the Research Fund—Flanders (FWO). Work performed in the laboratory of the authors was supported by research grants of the FWO, the Research Council of the KU Leuven and the Interuniversity Attraction Poles Programmes (Belgian Science Policy).

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    1. Laboratory for Molecular and Cellular Signaling, Department of Cellular and Molecular Medicine & Leuven Kanker Instituut, KU Leuven, Leuven, Belgium

      Gemma Roest, Rita M. La Rovere, Geert Bultynck & Jan B. Parys

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    1. MPI for Biophysical Chemistry, Göttingen, Germany

      Joachim Krebs

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    Roest, G., La Rovere, R.M., Bultynck, G., Parys, J.B. (2017). IP3 Receptor Properties and Function at Membrane Contact Sites. In: Krebs, J. (eds) Membrane Dynamics and Calcium Signaling. Advances in Experimental Medicine and Biology, vol 981. Springer, Cham. https://doi.org/10.1007/978-3-319-55858-5_7

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