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Rab7 is functionally required for selective cargo sorting at the early endosome.

Emmanuelle Girard1, Daniela Chmiest, Natalie Fournier

  • 1AP-HP (Assistance Publique - Hôpitaux de Paris), Hôpital Européen Georges Pompidou, Service de Biochimie, 75015, Paris, France; Université Paris-Sud, EA 4529, UFR de Pharmacie, 92296, Châtenay-Malabry, France; CNRS UMR144, 75248 Paris cedex 05, France; Institut Curie, Centre de Recherche, Laboratoire Trafic, Signalisation et Ciblage Intracellulaires, 75248, Paris Cedex 05, France.

Traffic (Copenhagen, Denmark)
|December 17, 2013
PubMed
Summary
This summary is machine-generated.

Rab7 protein is crucial for membrane trafficking, regulating both early and late endosomes. Its depletion impairs low-density lipoprotein (LDL) processing and the sorting of specific cargo proteins.

Keywords:
Rab7cholesterolendocytosisendosometrafficking

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Membrane Trafficking

Background:

  • Rab GTPases are key regulators of membrane trafficking.
  • Rab7 is primarily associated with late endosome to lysosome transport.
  • Its role in earlier endosomal trafficking steps remains debated.

Purpose of the Study:

  • To investigate the role of Rab7 in early endosomal trafficking.
  • To determine if Rab7 influences the sorting of specific cargo molecules at early endosomes.
  • To clarify the Rab5 to Rab7 exchange timing during endosomal maturation.

Main Methods:

  • Rab7 depletion and inactivation experiments.
  • Analysis of endosome morphology and size.
  • Tracking of internalized cargo molecules like low-density lipoproteins (LDL).
  • Assessment of receptor sorting and recycling.

Main Results:

  • Rab7 depletion caused enlargement of early and late endosomes.
  • Internalized LDL was retained in enlarged early endosomes, impairing processing.
  • Rab7 activity is essential for sorting mannose-6-phosphate receptor, interferon alpha-receptor, and Shiga toxin B-subunit.
  • EGF sorting and transferrin/LDL-R recycling were unaffected.

Conclusions:

  • Rab7 plays a significant role in selective cargo sorting at early endosomes, beyond its known function in late endosome-lysosome transport.
  • The Rab5 to Rab7 exchange occurs early in the endosomal maturation pathway.
  • Rab7 is essential for maintaining normal endosomal trafficking and function.