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. Author manuscript; available in PMC: 2016 Nov 21.
Published in final edited form as: Nat Rev Mol Cell Biol. 2015 Dec 2;17(2):69–82. doi: 10.1038/nrm.2015.8

Table 1.

Location, characteristics and proposed functions of mammalian and yeast ER–organelle MCS proteins

MCS proteins Characteristics Proposed function Refs
Mitochondria–ER
MFN2–MFN2 or MFN1–MFN2

  • MFN2, both ER and mitochondria localized by FM data

  • MFN1, localized to mitochondria

 Calcium (Ca2+) transfer at ER–mitochondrial contact sites 15
VDAC–GRP75–Ins(1,4,5)P3R

  • VDAC, outer mitochondrial membrane Ca2+-uptake channel

  • GRP75, soluble protein

  • Ins(1,4,5)P3R, ER integral membrane protein and ER Ca2+-release channel

 Ins(1,4,5)P3R is the Ca2+-release channel on the ER, when stimulated Ca2+ can be transferred to mitochondria at MCSs and taken up into the mitochondria through VDACs. The GRP75 chaperone couples the Ins(1,4,5)P3R and the VDAC 73, 81, 84
PTPIP51–VAPs

  • PTPIP51, outer mitochondrial membrane protein with PtdInsP-transfer domain

  • VAP, ER integral membrane protein

 Lipid transfer between ER and mitochondria may be facilitated by the PtdInsP-transfer domain of PTPIP51 114
FIS1–BAP31

  • FIS1, outer mitochondrial membrane protein

  • BAP31, ER integral membrane protein

 FIS1–BAP31 interaction allows for transmission of apoptotic signals from the mitochondria to the ER 115
Mmr1* Localizes to yeast cortical ER–mitochondria contact sites Important for mitochondrial inheritance into yeast bud 12
ERMES complex* Contains both ER- and mitochondria-localized proteins In yeast, tethers ER and mitochondria. ERMES components contain SMP domains that are potentially capable of transferring lipids 14,44, 46,47, 50
Endosome–ER
ORP1L–VAP-A

  • ORP1L associates with the late endosome membrane through RAB7

  • VAP, ER membrane protein

 Senses sterol levels and regulates endosome positioning. Under low cholesterol concentrations, ORP1L negatively regulates late endosome association with dynein. Dynein no longer translocates late endosomes to the cell centre 28
STARD3–VAP-A

  • STARD3, integral membrane protein in late endosomes

  • VAP, ER membrane protein

 Possible role in sterol sensing and endosome positioning 7, 59
STARD3NL–VAP-A

  • STARD3NL, integral membrane protein in late endosomes

  • VAP, ER membrane protein

 Possible role in sterol sensing and endosome tabulation 7
NPC1–ORP5

  • NPC1, integral membrane protein in late endosomes

  • ORP5, ER integral membrane protein

 Proposed mechanism for cholesterol transfer through late endosome–ER MCSs by the ORD domain of ORP5 58

  • RAB7–GTP, PI3P

  • Protrudin, VAP-A

  • RAB7–GTP and PI3P are inserted in the late endosome membrane

  • Protrudin, ER membrane protein with FFAT domain that interacts with VAP-A

 Regulates endosome positioning. Protrudin transfers kinesin-1 from the ER to late endosomes. Kinesin facilitates late endosome translocation to the cell periphery 34
EGFR–PTP1B

  • EGFR, receptor protein in the endosome membrane

  • PTP1B, ER-localized phosphatase

 PTP1B dephosphorylates receptors to regulate EGFR signalling 11
G-CSFR–PTP1B G-CSFR, receptor protein in the endosome membrane PTP1B, ER-localized phosphatase PTP1B dephosphorylates receptors to regulate G-CSFR signalling 116
Golgi–ER
OSBP–VAP OSBP associates with the Golgi membrane through PtdIns4P binding and contains a FFAT domain capable of interacting with ER VAPs OSBP regulates PtdIns(4)P levels in the Golgi by transferring PtdIns(4)P from Golgi to the ER. OSBP transfers sterol in the opposite direction, from ER to Golgi 60, 64
CERT–VAP CERT associates with the Golgi membrane through PtdIns(4)P binding and contains a FFAT domain capable of interacting with ER VAPs CERT has a role in ceramide transfer at ER–Golgi MCSs 60, 61
FAPP2–VAP FAPP2 associates with the Golgi membrane through PtdIns(4)P binding and contains a FFAT domain capable of interacting with ER VAPs FAPP2 has a role in glucosylceramide transfer at ER–Golgi MCSs 62
NIR2–VAP NIR2 associates with the Golgi membrane and contains a FFAT motif capable of interacting with ER VAPs NIR2 plays a part in maintaining diacylglycerol levels in the Golgi 60, 63, 60
Lipid droplet–ER
DGAT2–FATP1 DGAT2 localizes to lipid droplets FATP1 localizes to the ER DGAT2 and FATP1 coordinate lipid droplet expansion at lipid droplet–ER MCSs 117
Peroxisome–ER
Pex3–Inp1–Pex3* Pex3, integral membrane protein localized to both peroxisomes and ER Inp1 cytosolic factor In yeast, Inp3 binds to Pex3 and regulates tethering of peroxisomes to ER 118

CERT, ceramide-transfer protein; DGAT2, diacylglycerol O-acyltransferase 2; EGFR, epidermal growth factor receptor; ER, endoplasmic reticulum; ERMES, ER–mitochondrial encounter structure; FAPP2, four-phosphate adaptor protein 2; FATP1, fatty acid transport protein 1; FFAT, diphenylalanine in an acidic tract; FM, fluorescence microscopy; G-CSFR, granulocyte–macrophage colony-stimulating receptor; GRP75, glucose-regulated protein 75; Inp, inheritance of peroxisomes; Ins(1,4,5)P3R, inositol-1,4,5-trisphosphate receptor; LE, late endosome; MCS, membrane contact site; MFN, mitofusin; Mmr1, mitochondrial Myo2p receptor-related 1; NIR2, PYK2 N-terminal domain-interacting receptor 2; NPC1, Niemann–Pick C1 protein; ORD, oxysterol-binding-related domain; ORP, oxysterol-binding-related protein; Pex3, peroxin 3; PtdInsP, phosphatidylinositol phosphate; PTP1B, protein-Tyr phosphatase 1B; STARD3, START domain-containing protein 3; STARD3NL, STARD3 N-terminal-like protein; VAP, VAMP-associated protein; VDAC, voltage-dependent anion channel.

*

indicates yeast proteins, all other proteins are of mammalian origin.