Table 1.

Exemplary approaches and molecular tools for MCS visualization and perturbation

MCS location	Design/binding partners	Approach or tool	Reference
MCS visualization and labelling
ER–mitochondria	ER: split GFP strands 1–10 Mito: split GFP strand 11	BiFC	Yang et al. (2018)
ER–mitochondria	ER: VAP‐B Mito: PTPIP51	PLA	Gomez‐Suaga et al. (2017)
ER–LE	ER: VAP‐A LE: STARD3 or STARD3NL	PLA	Alpy et al. (2013)
ER–PM	Engineered ER‐resident Rit‐PB with spacers and linkers; GFP‐tagged	MAPPER	Chang et al. (2013)
Chemical or optogenetic actuators for tethering and MCS assembly
ER–mitochondria tethering	ER: CFP‐FRB‐Sac1 (521–587) Mito: mAKAP (34–63)‐FKBP‐RFP	Rapamycin‐inducible chemical dimerizer	Csordas et al. (2010)
ER–mitochondria tethering	ER: SspB‐mKate2‐CB5 Mito: Venus‐iLID‐ActA	iLID‐based optical dimerizer	Shi et al. (2018)
ER–PM MCS	ER‐anchored photosensitive GFP‐tagged Rit‐PB	LOV2‐based LiMETER	Jing et al. (2015)
ER–PM MCS	ER‐anchored photosensitive GFP‐ or mRuby2‐tagged STIM1‐PB and its variants	LOV2‐based OptoPBer	He et al. (2017)

Abbreviations: ActA, actin assembly inducing protein; BiFC, bimolecular fluorescence complementation; CB5, cytochrome b ₅; ER, endoplasmic reticulum; FKBP, FK506 binding protein; FRB domain, FKBP12‐rapamycin binding domain; iLID, improved light‐induced dimer; LE, late endosome; LiMETER, light‐inducible membrane tethered peripheral ER; LOV2, light‐oxygen‐voltage sensing domain 2; MAPPER, membrane‐attached peripheral ER; MCS, membrane contact site; PB, polybasic domain; PLA, proximity ligation assay; PM, plasma membrane; PTPIP51, protein tyrosine phosphatase interacting protein; STARD3, StAR related lipid transfer domain‐3; STARD3NL, STARD3 N‐terminal like; VAP, vesicle‐associated membrane protein‐associated protein.