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Unconventional endocytic mechanisms.

Henri-François Renard1, Emmanuel Boucrot2

  • 1Biochemistry and Cellular Biology Research Unit (URBC), Namur Research Institute for Life Science (NARILIS), University of Namur, Rue de Bruxelles 61, B-50000, Namur, Belgium.

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Summary

Endocytosis, the cell

Keywords:
Activity-dependent bulk endocytosisCargoesClathrinClathrin-independent carriers/GPI-AP-enriched early endosomal compartments (CLIC/GEEC)Clathrin-independent endocytosisClathrin-mediated endocytosisEGFR Non-Clathrin endocytosisEndocytosisEndophilin-A3/Galectin-8-mediated endocytosisFast endophilin-mediated endocytosis (FEME)Glycolipid-Lectin hypothesisGlycosylphosphatidylinositol-anchored proteinsInterleukin-2 receptor endocytosisLipidsMacropinocytosisMassive EndocytosisReceptorsUltrafast endocytosis

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Area of Science:

  • Cell Biology
  • Molecular Biology

Background:

  • Endocytosis is crucial for cellular functions, including nutrient uptake and pathogen entry.
  • Clathrin-mediated endocytosis (CME) is a primary pathway, but unconventional clathrin-independent endocytic (CIE) routes also exist.
  • Viruses, toxins, and bacteria exploit endocytosis for cellular infection.

Purpose of the Study:

  • To elucidate the diverse mechanisms of clathrin-independent endocytosis (CIE).
  • To categorize CIE routes based on their distinct molecular drivers and cargo.
  • To understand how pathogens utilize CIE for cellular entry.

Main Methods:

  • Review and synthesis of existing literature on endocytosis pathways.
  • Categorization of CIE mechanisms based on membrane remodeling, cargo capture, and pit formation.
  • Analysis of specific examples of CIE, including viral and toxin uptake.

Main Results:

  • CIE pathways utilize distinct mechanisms: signaling-induced membrane remodeling (macropinocytosis, ADBE, MEND, EGFR-NCE), cytosolic protein-mediated cargo capture (FEME, IL-2Rβ endocytosis, ultrafast endocytosis), and lipid/cargo clustering (GL-Lect hypothesis).
  • These CIE routes mediate the uptake of specific cargoes like viruses (SV40), toxins (Shiga, cholera), and clustered receptors.
  • Specific CIE pathways identified include CLIC/GEEC and endophilin-A3-mediated CIE.

Conclusions:

  • Multiple clathrin-independent endocytosis pathways operate in parallel to CME.
  • These diverse CIE routes are essential for specific cellular functions and are exploited by pathogens.
  • Understanding CIE mechanisms is critical for cell biology and combating infectious diseases.