4.4 Review

Sorting of cargo in the tubular endosomal network

Journal

BIOESSAYS
Volume 44, Issue 12, Pages -

Publisher

WILEY
DOI: 10.1002/bies.202200158

Keywords

adaptor proteins; endocytosis; membrane fission; membrane fusion; Rab proteins; recycling endosomes; Sec1; Munc18 protein; small GTPases; SNAREs; tether; tubular endosomal networks; vesicle transport

Funding

  1. Swiss National Science Foundation [310030_197779, CRSII3_141956]
  2. University of Basel
  3. Swiss National Science Foundation (SNF) [CRSII3_141956, 310030_197779] Funding Source: Swiss National Science Foundation (SNF)

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Intercellular communication is a necessary process in multicellular organisms, where molecules secreted by one cell bind to a receptor on another cell. The fate of the receptor-ligand complex and other endocytosed proteins is determined by the cell, with the majority being recycled back to the plasma membrane and the rest being degraded in the lysosome. This review summarizes the current understanding of the mechanism behind recycling cargo sorting and proposes a model of differential affinities between cargo and cargo receptors/adaptors for iterative sorting in endosomes.
Intercellular communication is an essential process in all multicellular organisms. During this process, molecules secreted by one cell will bind to a receptor on the cognate cell leading to the subsequent uptake of the receptor-ligand complex. Once inside, the cell then determines the fate of the receptor-ligand complex and any other proteins that were endocytosed together. Approximately 80% of endocytosed material is recycled back to the plasma membrane either directly or indirectly via the Golgi apparatus and the remaining 20% is delivered to the lysosome for degradation. Although most pathways have been identified, we still lack understanding on how specificity in sorting of recycling cargos into different pathways is achieved, and how the cell reaches high accuracy of these processes in the absence of clear sorting signals in the bulk of the client proteins. In this review, we will summarize our current understanding of the mechanism behind recycling cargo sorting and propose a model of differential affinities between cargo and cargo receptors/adaptors with regards to iterative sorting in endosomes.

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