The ER phagosome connection in the era of membrane contact sites

Abstract

Phagocytosis is an essential mechanism through which innate immune cells ingest foreign material that is either destroyed or used to generate and present antigens and initiate adaptive immune responses. While a role for the ER during phagosome biogenesis has been recognized, whether fusion with ER cisternae or vesicular derivatives occurs has been the source of much contention. Membrane contact sites (MCS) are tight appositions between ER membranes and various organelles that coordinate multiple functions including localized signalling, lipid transfer and trafficking. The discovery that MCS form between the ER and phagosomes now begs the question of whether MCS play a role in connecting the ER to phagosomes under different contexts. In this review, we consider the implications of MCS between the ER and phagosomes during cross-presentation and infection with intracellular pathogens. We also discuss the similarities between these contacts and those between the ER and plasma membrane and acidic organelles such as endosomes and lysosomes. This article is part of a Special Issue entitled: Membrane Contact Sites edited by Christian Ungermann and Benoit Kornmann.

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 , ).…”

“…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.…”

Stress Coping Strategies in the Heart: An Integrated View

“…Moreover, synthesis of cellular lipids involves the activities of enzymes resident in the ER, mitochondria, and peroxisomes ( 42 ). Coordination of these cellular processes is achieved in part through membrane contact sites (MCS), which are formed between closely apposed organellar membranes including the plasma membrane (Figure 2 ) ( 43 – 50 ).…”

A guide to measuring phagosomal dynamics

“…While it is widely known that phagosomes undergo a sequential series of fusion and fission events with endosomes and lysosomes [17,18] (Fig. 1), it has become increasingly apparent that phagosomes also interact with several other organelles such as the endoplasmic reticulum (ER) [19], mitochondria [20,21], and the trans-Golgi network (TGN) [22] (Fig. 2).…”