Journal
JOURNAL OF PHYSIOLOGY-LONDON
Volume 598, Issue 9, Pages 1725-1739Publisher
WILEY
DOI: 10.1113/JP277761
Keywords
Membrane contact sites; MCSs visualization; MCSs manipulation; Calcium homeostasis; lipid metabolism; organelle remodeling; fluorescence; optogenetics
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Funding
- NCI NIH HHS [R01 CA232017] Funding Source: Medline
- NHLBI NIH HHS [R01 HL134780] Funding Source: Medline
- NIGMS NIH HHS [R21 GM126532, R01 GM112003] Funding Source: Medline
- NIH HHS [R21GM126532, R01HL146852, R01CA232017] Funding Source: Medline
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Membrane contact sites (MCSs) are specialized subcellular compartments formed by closely apposed membranes from two organelles. The intermembrane gap is separated by a distance ranging from 10 to 35 nm. MCSs are typically maintained through dynamic protein-protein and protein-lipid interactions. These intermembrane contact sites constitute important intracellular signalling hotspots to mediate a plethora of cellular processes, including calcium homeostasis, lipid metabolism, membrane biogenesis and organelle remodelling. In recent years, a series of genetically encoded probes and chemogenetic or optogenetic actuators have been invented to aid the visualization and interrogation of MCSs in both fixed and living cells. These molecular tools have greatly accelerated the pace of mechanistic dissection of membrane contact sites at the molecular level. In this review, we present an overview on the latest progress in this endeavour, and provide a general guide to the selection of methods and molecular tools for probing interorganellar membrane contact sites.
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