ABSTRACT
The endoplasmic reticulum (ER) is the largest organelle in the cell, and its functions have been studied for decades. The past several years have provided novel insights into the existence of distinct domains between the ER and other organelles, known as membrane contact sites (MCSs). At these contact sites, organelle membranes are closely apposed and tethered, but do not fuse. Here, various protein complexes can work in concert to perform specialized functions such as binding, sensing and transferring molecules, as well as engaging in organelle biogenesis and dynamics. This Review describes the structure and functions of MCSs, primarily focusing on contacts of the ER with mitochondria and endosomes.
Subject(s)
Endoplasmic Reticulum/metabolism , Endoplasmic Reticulum/ultrastructure , Eukaryotic Cells/metabolism , Membrane Proteins/metabolism , Saccharomyces cerevisiae/metabolism , Saccharomyces cerevisiae/ultrastructure , Animals , Biological Transport , Calcium/metabolism , Cell Membrane/chemistry , Cell Membrane/metabolism , Cell Membrane/ultrastructure , Endoplasmic Reticulum/chemistry , Endosomes/chemistry , Endosomes/metabolism , Endosomes/ultrastructure , Eukaryotic Cells/ultrastructure , Gene Expression Regulation , Humans , Lipid Metabolism , Membrane Proteins/chemistry , Membrane Proteins/genetics , Mitochondria/chemistry , Mitochondria/metabolism , Mitochondria/ultrastructure , Mitochondrial Membranes/chemistry , Mitochondrial Membranes/metabolism , Mitochondrial Membranes/ultrastructure , Organelle Biogenesis , Saccharomyces cerevisiae/geneticsABSTRACT
Endocytic cargo and Rab GTPases are segregated to distinct domains of an endosome. These domains maintain their identity until they undergo fission to traffic cargo. It is not fully understood how segregation of cargo or Rab proteins is maintained along the continuous endosomal membrane or what machinery is required for fission. Endosomes form contact sites with the endoplasmic reticulum (ER) that are maintained during trafficking. Here, we show that stable contacts form between the ER and endosome at constricted sorting domains, and free diffusion of cargo is limited at these positions. We demonstrate that the site of constriction and fission for early and late endosomes is spatially and temporally linked to contact sites with the ER. Lastly, we show that altering ER structure and dynamics reduces the efficiency of endosome fission. Together, these data reveal a surprising role for ER contact in defining the timing and position of endosome fission.
