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The recycling endosome, also known as the endosomal recycling compartment (ERC), is a part of the slow-recycling process of the endocytic pathway. Molecules internalized through receptor-mediated endocytosis are either degraded in the lysosomes or are recycled to the plasma membrane through the fast- or slow-recycling route.
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The early endosome containing internalized molecules matures through transformations in its location, morphology, intraluminal pH, and membrane protein composition. Together, these changes result in a more acidic late endosome that contains multiple intraluminal vesicles; therefore, the late endosome is also called a multivesicular body (MVB).
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Coordination between ESCRT function and Rab conversion during endosome maturation.

Daniel P Ott1, Samit Desai1, Jachen A Solinger1

  • 1Biozentrum, University of Basel, Basel, Switzerland.

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Summary
This summary is machine-generated.

Early ESCRT proteins and ubiquitinated cargo control endosome maturation by timing Rab5-to-Rab7 conversion, ensuring proper cell signaling and homeostasis.

Keywords:
C. elegansEndosomesLive Cell ImagingMammalian CellsRab GTPases

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Area of Science:

  • Cell Biology
  • Molecular Biology

Background:

  • The endosomal pathway regulates cell signaling and homeostasis.
  • Rab5 marks early endosomes, while Rab7 marks late endosomes destined for lysosomal fusion.
  • The coordination between ESCRT-mediated intraluminal vesicle formation and Rab conversion is unclear.

Purpose of the Study:

  • To investigate the relationship between ESCRT function and Rab5-to-Rab7 conversion during endosome maturation.
  • To elucidate the role of ubiquitinated cargo in this process.

Main Methods:

  • Studied the effects of early ESCRT loss on endosome morphology and Rab conversion.
  • Manipulated ubiquitinated cargo levels.
  • Investigated the localization and function of Rab5 and Rab7 guanine nucleotide exchange factors (GEFs).

Main Results:

  • Loss of early ESCRTs caused enlarged Rab5 endosomes and blocked Rab conversion.
  • Reducing ubiquitinated cargo rescued this phenotype.
  • Ubiquitinated proteins on endosomes prevented Rab7 GEF (SAND-1/CCZ-1) displacement of Rab5 GEF (RABX-5).
  • Rab7 overexpression partially bypassed the block, suggesting an alternative Rab7 GEF.

Conclusions:

  • ESCRT-mediated cargo corralling precedes and regulates Rab conversion.
  • Ubiquitinated cargo and ESCRT-0 act as timers for Rab conversion onset.
  • This reveals a hierarchical pathway essential for endosomal trafficking and cellular homeostasis.