Mobile late endosomes modulate peripheral endoplasmic reticulum network architecture

Abstract

The endoplasmic reticulum (ER) is the largest organelle contacting virtually every other organelle for information exchange and control of processes such as transport, fusion, and fission. Here, we studied the role of the other organelles on ER network architecture in the cell periphery. We show that the co‐migration of the ER with other organelles, called ER hitchhiking facilitated by late endosomes and lysosomes is a major mechanism controlling ER network architecture. When hitchhiking occurs, emerging ER structures may fuse with the existing ER tubules to alter the local ER architecture. This couples late endosomal/lysosomal positioning and mobility to ER network architecture. Conditions restricting late endosomal movement—including cell starvation—or the depletion of tether proteins that link the ER to late endosomes reduce ER dynamics and limit the complexity of the peripheral ER network architecture. This indicates that among many factors, the ER is controlled by late endosomal movement resulting in an alteration of the ER network architecture.

Intertwined and Finely Balanced: Endoplasmic Reticulum Morphology, Dynamics, Function, and Diseases

“…Furthermore, in cultured neurons, the ER extends all along axons, yet kinectin is only observed in the cell body [ 194 ], in keeping with its proposed role in maintaining ER sheet spacing [ 13 ]. Nevertheless, the siRNA depletion of kinectin decreased ER network dynamics in Cos-7 cells [ 26 ]. Intriguingly, Rab10, is also implicated in regulating ER tubule formation [ 7 ] and has been reported to form a complex with JIP1, a neuronally expressed kinesin adaptor, and KLC1, to promote the transport of secretory vesicles during neuronal polarisation and axon growth [ 201 ].…”

“…In addition to tubule extension driven by motors directly at the ER membrane, ER dynamics can be caused by ER membrane contact sites with early and late endosomes, lysosomes, and mitochondria [ 22 , 26 , 38 , 74 , 75 , 84 , 85 , 86 , 204 , 219 , 220 ] that move along microtubules. This is an example of a process referred to as ‘hitchhiking’, where one organelle provides the motor and drives the movement of another cargo that is not motile by itself [ 38 , 221 , 222 ].…”

“…Historically, tubule extension speeds have been measured [ 20 , 21 , 22 , 23 ], but the quantification of other aspects of ER dynamics has been challenging due to limitations in microscopy and computation. Recently, software designed to analyse the motion of the ER in live cells has been published [ 24 , 25 , 26 , 27 ] and further developments in this area are likely in the near future.…”

PxdA interacts with the DipA phosphatase to regulate peroxisome hitchhiking on early endosomes

“…In U. maydis, LDs and the endoplasmic reticulum, as well as peroxisomes, hitchhike on EEs ( Guimaraes et al , 2015 ), although U. maydis lacks a PxdA homologue ( Steinberg, 2016 ). Recently, mRNAs, peroxisomes and the endoplasmic reticulum have also been shown to hitchhike on endolysosomal membranes in mammalian cells ( Guo et al ., 2018 ; Liao et al , 2019 ; Spits et al ., 2021 ).…”

What the VAP: The Expanded VAP Family of Proteins Interacting With FFAT and FFAT-Related Motifs for Interorganellar Contact

“…Eukaryotic life is defined by the presence of membranelimited organelles that are specialized in a multitude of biochemical processes. These organelles need to communicate with each other at membrane contact sites (MCS) to function properly ( Wu et al, 2006 ; Rowland et al, 2014 ; Cabukusta and Neefjes, 2018 ; Spits et al, 2021 ). MCS are intracellular regions where two organelles are closely juxtaposed to form an intracellular synapse to facilitate interorganellar communication and metabolic exchange ( Eisenberg-Bord et al, 2016 ; Gatta and Levine, 2017 ; Scorrano et al, 2019 ).…”