ER–endosome contact sites in endosome positioning and protrusion outgrowth

Abstract

The endoplasmic reticulum (ER) makes abundant contacts with endosomes, and the numbers of contact sites increase as endosomes mature. It is already clear that such contact sites have diverse compositions and functions, but in this mini-review we will focus on two particular types of ER-endosome contact sites that regulate endosome positioning. Formation of ER-endosome contact sites that contain the cholesterol-binding protein oxysterol-binding protein-related protein 1L (ORP1L) is coordinated with loss of the minus-end-directed microtubule motor Dynein from endosomes. Conversely, formation of ER-endosome contact sites that contain the Kinesin-1-binding protein Protrudin results in transfer of the plus-end-directed microtubule motor Kinesin-1 from ER to endosomes. We discuss the possibility that formation of these two types of contact sites is coordinated as a 'gear-shift' mechanism for endosome motility, and we review evidence that Kinesin-1-mediated motility of late endosomes (LEs) to the cell periphery promotes outgrowth of neurites and other protrusions.

Mechanisms and functions of lysosome positioning

“…An alternative mechanism for coupling of late endosomes to kinesin-1 involves the ER-anchored protein protrudin, which binds simultaneously to the small GTPase Rab7 (which has two isoforms in mammals, Rab7a and Rab7b, hereafter generically referred to as Rab7) and phosphatidylinositol 3-phosphate [PtdIns (3)P] to bridge the ER and lysosomal membranes. Protrudin then transfers late endosomes to the Rab7 effector FYVE-and coiledcoil-domain-containing protein (FYCO1) and kinesin-1 for late endosome movement towards the cell periphery (Matsuzaki et al, 2011;Raiborg et al, 2016) (Fig. 4).…”

The EGFR odyssey – from activation to destruction in space and time

“…Incidentally, VAPA/B also interacts with the ER-associated protein protrudin, which is capable of loading kinesin-1 motor onto Rab7-FYCO1 (Raiborg et al, 2015). It has been speculated that this scenario presents an opportunity for Rab7 to switch the direction of endosomal transport away from the nucleus (Wijdeven et al, 2015;Raiborg et al, 2016). Although EGFR-containing late endosomes have not been shown to travel via this plus-enddirected route, whether and how Rab7, or its associated proteins, may 'guard' against the misdirection of EGFR is an important issue that remains largely unexplored.…”

VAPB depletion alters neuritogenesis and phosphoinositide balance in motoneuron-like cells: relevance to VAPB-linked amyotrophic lateral sclerosis

“…Hence, we propose that a PI4P build-up on post-Golgi vesicles of differentiating NSC34 cells may diminish their capacity to undergo exocytosis, thus delaying the process of plasma membrane expansion required for neuritogenesis. It is currently thought that a population of late endosomes is involved in delivering membrane to the cell surface during neuritogenesis (Raiborg et al, 2015(Raiborg et al, , 2016Sann et al, 2009); thus, the PI4P-containing acidic vesicles observed in the silenced clones could represent stalled intermediates on their way to fusion with the plasma membrane. Whether the PI4P build-up in these vesicles is a consequence of the PI4P overload in the TGN, or a direct consequence of the absence of VAPB at ER-endolysosome contact sites, remains to be established.…”