Lipids at membrane contact sites: cell signaling and ion transport

Abstract

Communication between organelles is essential to coordinate cellular functions and the cell's response to physiological and pathological stimuli. Organellar communication occurs at membrane contact sites (MCSs), where the endoplasmic reticulum (ER) membrane is tethered to cellular organelle membranes by specific tether proteins and where lipid transfer proteins and cell signaling proteins are located. MCSs have many cellular functions and are the sites of lipid and ion transfer between organelles and generation of second messengers. This review discusses several aspects of MCSs in the context of lipid transfer, formation of lipid domains, generation of Ca and cAMP second messengers, and regulation of ion transporters by lipids.

VAP‐SCRN1 interaction regulates dynamic endoplasmic reticulum remodeling and presynaptic function

“…Considering that VAPs are best known to act as major ER receptors by facilitating tight membrane contact sites between the ER and other organelles, it is tempting to speculate that these membrane contact sites might be engaged in controlling VAP-mediated functions on ER integrity and dynamics (Muallem et al, 2017;Wu et al, 2018). Here, we identified the VAP-SCRN1 interactions as critical regulators for maintaining ER structure and dynamics.…”

Anoctamin 8 tethers endoplasmic reticulum and plasma membrane for assembly of Ca 2+ signaling complexes at the ER/PM compartment

“…Information and material flow between cellular compartments and organelles must occur with high fidelity to ensure coordination among all cellular processes. For faithful information flow, cells use membrane contact sites (MCSs) between the ER that spans the entire cell interior and all other cellular membranes (Lahiri et al , ; Chung et al , ; Marchi et al , ; Muallem et al , ; Nunes‐Hasler & Demaurex, ). MCSs are formed by tether proteins that are anchored in the ER, either directly or through VAP proteins (Murphy & Levine, ), with cytoplasmic domains that span the distance between the ER and the target membranes they interact with (Muallem et al , ).…”

“…For faithful information flow, cells use membrane contact sites (MCSs) between the ER that spans the entire cell interior and all other cellular membranes (Lahiri et al , ; Chung et al , ; Marchi et al , ; Muallem et al , ; Nunes‐Hasler & Demaurex, ). MCSs are formed by tether proteins that are anchored in the ER, either directly or through VAP proteins (Murphy & Levine, ), with cytoplasmic domains that span the distance between the ER and the target membranes they interact with (Muallem et al , ). These features are present in the ER/PM junction tethers E‐Syts (Giordano et al , ), GRAM domain proteins (Besprozvannaya et al , ), and the yeast Ist2 (Maass et al , ).…”

“…Such an arrangement is essential to generate spatially and temporally precise Ca 2+ signals to modulate specific cellular activity at the site where the Ca 2+ signal is evoked (Park et al , ; Ahuja et al , ). It is now clear that compartmentation of cell signaling is achieved by targeting signaling proteins to membrane contact sites (MCSs; Lahiri et al , ; Chung et al , ; Marchi et al , ; Muallem et al , ; Nunes‐Hasler & Demaurex, ). MCSs are formed between the ER and all cellular organelles, including the mitochondria (Marchi et al , ) and the PM (Henne et al , ; Chung et al , ), by tether proteins.…”

A toolbox for the immunomagnetic purification of signaling organelles

“…Presence of RibS3 in the 0 minutes magnetic fraction may be explained by unspecific enclosure of ribosomes in resealed membrane sheets. The ER marker protein ERp72 is present in all magnetic fractions which is probably due to the fact that ER is involved also in internalization of cargo and ER contact site with most other organelles have been described . Thus, ER is probably present in most organelle separations.…”