Abstract
The compartmentalisation achieved by confining cytoplasm into membrane-enclosed organelles in eukaryotic cells is essential for maintaining vital functions including ATP production, synthetic and degradative pathways. While intracellular organelles are highly specialised in these functions, the restricting membranes also impede exchange of molecules responsible for the synchronised and responsive cellular activities. The initial identification of contact sites between the ER and plasma membrane (PM) provided a potential candidate structure for communication between organelles without mixing by fusion. Over the past decades, research has revealed a far broader picture of the events. Membrane contact sites (MCSs) have been recognized as increasingly important actors in cell differentiation, plasticity and maintenance, and, upon dysfunction, responsible for pathological conditions such as cancer and neurodegenerative diseases. Present in multiple organelles and cell types, MCSs promote transport of lipids and Ca2+ homoeostasis, with a range of associated protein families. Interestingly, each MCS displays a unique molecular signature, adapted to organelle functions. This review will explore the literature describing the molecular components and interactions taking place at ER-PM contact sites, their functions, and implications in eukaryotic cells, particularly neurons, with emphasis on lipid transfer proteins and emerging function of SNAREs.
Highlights
A distinctive property of eukaryotic cells is the compartmentaliasation of the cytoplasm by intracellular membranes
VAMP-associated proteins or VAPs are another family suggested to act as tethers at Membrane contact sites (MCSs), with orthologues identified in plants (Siao et al, 2016) and yeast (Loewen et al, 2003)
The study of MCSs has grown tremendously in the last 20 years, our understanding of their structure and functions still shows many gaps. Much of this difficulty arises from the inherent features of MCSs; they are minute, dynamic structures with diverse molecular compositions between organelles and organisms and can be difficult to study
Summary
A distinctive property of eukaryotic cells is the compartmentaliasation of the cytoplasm by intracellular membranes. ER-mediated contacts sites have been shown to facilitate Ca2+ homoeostasis (Wu et al, 2006) lipid transport (Tavassoli et al, 2013), modulate autophagic biogenesis (Nascimbeni et al, 2017), organelle morphology (Manford et al, 2012), and excitability in neurons and muscle cells (Ito et al, 2001; Sahu et al, 2019).
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