Unconventional endocytic mechanisms

Henri François Renard, Emmanuel Boucrot

Research output: Contribution to journalReview articlepeer-review


Endocytosis mediates the uptake of extracellular proteins, micronutrients and transmembrane cell surface proteins. Importantly, many viruses, toxins and bacteria hijack endocytosis to infect cells. The canonical pathway is clathrin-mediated endocytosis (CME) and is active in all eukaryotic cells to support critical house-keeping functions. Unconventional mechanisms of endocytosis exit in parallel of CME, to internalize specific cargoes and support various cellular functions. These clathrin-independent endocytic (CIE) routes use three distinct mechanisms: acute signaling-induced membrane remodeling drives macropinocytosis, activity-dependent bulk endocytosis (ADBE), massive endocytosis (MEND) and EGFR non-clathrin endocytosis (EGFR-NCE). Cargo capture and local membrane deformation by cytosolic proteins is used by fast endophilin-mediated endocytosis (FEME), IL-2Rβ endocytosis and ultrafast endocytosis at synapses. Finally, the formation of endocytic pits by clustering of extracellular lipids or cargoes according to the Glycolipid-Lectin (GL-Lect) hypothesis mediates the uptake of SV40 virus, Shiga and cholera toxins, and galectin-clustered receptors by the CLIC/GEEC and the endophilin-A3-mediated CIE.

Original languageEnglish
Pages (from-to)120-129
Number of pages10
JournalCurrent Opinion in Cell Biology
Early online date13 Apr 2021
Publication statusPublished - Aug 2021


  • Activity-dependent bulk endocytosis
  • Cargoes
  • Clathrin
  • Clathrin-independent carriers/GPI-AP-enriched early endosomal compartments (CLIC/GEEC)
  • Clathrin-independent endocytosis
  • Clathrin-mediated endocytosis
  • EGFR Non-Clathrin endocytosis
  • Endocytosis
  • Endophilin-A3/Galectin-8-mediated endocytosis
  • Fast endophilin-mediated endocytosis (FEME)
  • Glycolipid-Lectin hypothesis
  • Glycosylphosphatidylinositol-anchored proteins
  • Interleukin-2 receptor endocytosis
  • Lipids
  • Macropinocytosis
  • Massive Endocytosis
  • Receptors
  • Ultrafast endocytosis


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