FBP17 and CIP4 recruit SHIP2 and lamellipodin to prime the plasma membrane for fast endophilin-mediated endocytosis

Nat Cell Biol. 2018 Sep;20(9):1023-1031. doi: 10.1038/s41556-018-0146-8. Epub 2018 Jul 30.

Abstract

Endocytosis mediates the cellular uptake of micronutrients and the turnover of plasma membrane proteins. Clathrin-mediated endocytosis is the major uptake pathway in resting cells1, but several clathrin-independent endocytic routes exist in parallel2,3. One such pathway, fast endophilin-mediated endocytosis (FEME), is not constitutive but triggered upon activation of certain receptors, including the β1 adrenergic receptor4. FEME activates promptly following stimulation as endophilin is pre-enriched by the phosphatidylinositol-3,4-bisphosphate-binding protein lamellipodin4,5. However, in the absence of stimulation, endophilin foci abort and disassemble after a few seconds. Looking for additional proteins involved in FEME, we found that 20 out of 65 BAR domain-containing proteins tested colocalized with endophilin spots. Among them, FBP17 and CIP4 prime the membrane of resting cells for FEME by recruiting the 5'-lipid phosphatase SHIP2 and lamellipodin to mediate the local production of phosphatidylinositol-3,4-bisphosphate and endophilin pre-enrichment. Membrane-bound GTP-loaded Cdc42 recruits FBP17 and CIP4, before being locally deactivated by RICH1 and SH3BP1 GTPase-activating proteins. This generates the transient assembly and disassembly of endophilin spots, which lasts 5-10 seconds. This mechanism periodically primes patches of the membrane for prompt responses upon FEME activation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Membrane / metabolism*
  • Endocytosis*
  • Fatty Acid-Binding Proteins
  • GTPase-Activating Proteins / genetics
  • GTPase-Activating Proteins / metabolism
  • HEK293 Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Minor Histocompatibility Antigens / genetics
  • Minor Histocompatibility Antigens / metabolism*
  • Phosphatidylinositol Phosphates / metabolism
  • Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases / genetics
  • Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases / metabolism*
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Rats
  • Signal Transduction
  • Time Factors
  • cdc42 GTP-Binding Protein / genetics
  • cdc42 GTP-Binding Protein / metabolism

Substances

  • ARHGAP17 protein, human
  • Carrier Proteins
  • FNBP1 protein, human
  • Fatty Acid-Binding Proteins
  • GTPase-Activating Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Minor Histocompatibility Antigens
  • Phosphatidylinositol Phosphates
  • RAPH1 protein, human
  • SH3BP1 protein, human
  • SH3GL1 protein, human
  • TRIP10 protein, human
  • phosphatidylinositol 3,4-diphosphate
  • INPPL1 protein, human
  • Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
  • CDC42 protein, human
  • cdc42 GTP-Binding Protein