Roles for ER:endosome membrane contact sites in ligand-stimulated intraluminal vesicle formation.

Louise H Wong,Emily R Eden,Clare E Futter

doi:10.1042/bst20170432

Louise H Wong, Emily R Eden + Show 1 more

Open Access

https://doi.org/10.1042/bst20170432

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Abstract

Multivesicular endosomes/bodies (MVBs) sort membrane proteins between recycling and degradative pathways. Segregation of membrane proteins onto intraluminal vesicles (ILVs) of MVBs removes them from the recycling pathway and facilitates their degradation following fusion of MVBs with lysosomes. Sorting of many cargos onto ILVs depends on the ESCRT (Endosomal Sorting Complex Required for Transport) machinery, although ESCRT-independent mechanisms also exist. In mammalian cells, efficient sorting of ligand-stimulated epidermal growth factor receptors onto ILVs also depends on the tyrosine phosphatase, PTP1B, an ER-localised enzyme that interacts with endosomal targets at membrane contacts between MVBs and the ER. This review focuses on the potential roles played by ER:MVB membrane contact sites in regulating ESCRT-dependent ILV formation.

Highlights

ESCRT (Endosomal Sorting Complex Required for Transport)-dependent sorting of ubiquitinated epidermal growth factor (EGF) receptor (EGFR) onto intraluminal vesicles (ILVs) of multivesicular endosomes/bodies (MVBs) plays an important role in down-regulation of EGFR signalling by removing the catalytic domain of the receptor from the cytoplasm and targeting the receptor for degradation
This is unlikely to be the sole explanation of enhanced ILV formation in EGF-stimulated cells because we have identified two proteins, annexin A1 and protein tyrosine phosphatase 1B (PTP1B), that are not normally considered part of the ESCRT machinery, but are absolute requirements for EGF-stimulated ILV formation [1,5]
We showed that the calcium and phospholipidbinding protein, annexin A1, associated with EGFR-containing MVBs where it underwent EGF-stimulated phosphorylation [7] and found that annexin A1 depletion or knockout had no effect on ILV formation in resting cells, but abolished EGF-stimulated ILV formation [1]

Summary

Review Article

Roles for ER:endosome membrane contact sites in ligand-stimulated intraluminal vesicle formation. Multivesicular endosomes/bodies (MVBs) sort membrane proteins between recycling and degradative pathways. Segregation of membrane proteins onto intraluminal vesicles (ILVs) of MVBs removes them from the recycling pathway and facilitates their degradation following fusion of MVBs with lysosomes. Sorting of many cargos onto ILVs depends on the ESCRT (Endosomal Sorting Complex Required for Transport) machinery, ESCRT-independent mechanisms exist. Efficient sorting of ligand-stimulated epidermal growth factor receptors onto ILVs depends on the tyrosine phosphatase, PTP1B, an ER-localised enzyme that interacts with endosomal targets at membrane contacts between MVBs and the ER. This review focuses on the potential roles played by ER:MVB membrane contact sites in regulating ESCRT-dependent ILV formation

Introduction

How do membrane contact sites regulate ILV formation?

Endosome fission

Findings

Potential future directions