Illuminating the membrane contact sites between the endoplasmic reticulum and the trans‐Golgi network

Abstract

Membrane contact sites (MCSs) between different organelles have been identified and extensively studied over the last decade. Several classes of MCSs have now well‐established roles, although the contacts between the endoplasmic reticulum (ER) and the trans‐side of the Golgi network (TGN) have long remained elusive. Until recently, the study of ER–TGN contact sites has represented a major challenge in the field, as a result of the lack of suitable visualization and isolation techniques. Only in the last 5 years has the combination of advanced technologies and innovative approaches permitted the identification of new molecular players and the functions of ER–TGN MCSs that couple lipid metabolism and anterograde transport. Although much has yet to be discovered, it is now established that ER–TGN MCSs control phosphatidyl‐4‐phosphate homeostasis by coupling the cis and the trans activity of the ER‐resident 4‐phosphatase Sac1. In this review, we focus on recent advances on the composition and function of ER–TGN MCSs.

Golgi Apparatus Regulates Plasma Membrane Composition and Function

“…Lipid transport proteins that bind and transfer individual lipids across MCS play an important role in this process [37]. MCS is defined as close apposition between the membranes of two organelles (<30 nm apart) that promotes the tethering of the membranes but not fusion so that the individual identity of the organelle is maintained [38]. The major membrane contact site operating at the secretory pathway is the one between ER and the TGN.…”

The Fast and the Furious: Golgi Contact Sites

“…NIR2 was shown to be required for Golgi targeting of OSBP and CERT ( Peretti et al, 2008 ), probably due to its PI–PI4P exchange activity at ER–Golgi contacts. However, NIR2’s contribution to PI transport at ER–Golgi contacts is still under debate ( Hanada, 2020 ; Masone et al, 2019 ).…”

“…In this review, we will discuss what has already been gleaned about Golgi contacts ( Masone et al 2019 ; Mesmin et al 2019 ) and what is still unknown. We will also discuss why we believe that the study and discovery of Golgi contacts have lagged behind those of other organelles, debating whether the Golgi really mediates fewer contacts or whether this phenomenon results from technical hindrances that have contributed to its underrepresentation in the contact site literature.…”

Maintaining social contacts: The physiological relevance of organelle interactions

“…So far, no integral Golgi proteins have been identified as ER-TGN tethers, however all known cytoplasmic tether components contain PH domains that preferentially bind the phosphoinositide PI(4)P, which is enriched at the TGN membrane [ 219 ]. The nature and functions of ER-Golgi MCSs are likely to vary between different organisms, due to large variations in the structure and arrangement of the Golgi across eukaryotes [ 220 ]. ER-Golgi MCSs have been extensively reviewed (see [ 20 , 215 , 220 , 221 ]), but some of the identified physiological functions will be briefly discussed here.…”

“…The nature and functions of ER-Golgi MCSs are likely to vary between different organisms, due to large variations in the structure and arrangement of the Golgi across eukaryotes [ 220 ]. ER-Golgi MCSs have been extensively reviewed (see [ 20 , 215 , 220 , 221 ]), but some of the identified physiological functions will be briefly discussed here.…”