Phosphatidylinositol-4,5-bisphosphate is required for endocytic coated vesicle formation

Matthias Jost, Fiona Simpson, Jennifer M. Kavran, Mark A. Lemmon, Sandra L. Schmid

Research output: Contribution to journalArticle

186 Scopus citations

Abstract

Receptor-mediated endocytosis via clathrin-coated vesicles has been extensively studied and, while many of the protein players have been identified, much remains unknown about the regulation of coat assembly and the mechanisms that drive vesicle formation [1]. Some components of the endocytic machinery interact with inositol polyphosphates and inositol lipids in vitro, implying a role for phosphatidylinositols in vivo [2,3]. Specifically, the adaptor protein complex AP2 binds phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2), PtdIns(3)P, PtdIns(3,4,5)P3 and inositol phosphates. Phosphatidylinositol binding regulates AP2 self-assembly and the interactions of AP2 complexes with clathrin and with peptides containing endocytic motifs [4,5]. The GTPase dynamin contains a pleckstrin homology (PH) domain that binds PtdIns(4,5)P2 and PtdIns(3,4,5)P3 to regulate GTPase activity in vitro [6,7]. However, no direct evidence for the involvement of phosphatidylinositols in clathrin-mediated endocytosis exists to date. Using well-characterized PH domains as high affinity and high specificity probes in combination with a perforated cell assay that reconstitutes coated vesicle formation, we provide the first direct evidence that PtdIns(4,5)P2 is required for both early and late events in endocytic coated vesicle formation.

Original languageEnglish (US)
Pages (from-to)1399-1404
Number of pages6
JournalCurrent Biology
Volume8
Issue number25
DOIs
StatePublished - Dec 31 1998

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Fingerprint Dive into the research topics of 'Phosphatidylinositol-4,5-bisphosphate is required for endocytic coated vesicle formation'. Together they form a unique fingerprint.

  • Cite this

    Jost, M., Simpson, F., Kavran, J. M., Lemmon, M. A., & Schmid, S. L. (1998). Phosphatidylinositol-4,5-bisphosphate is required for endocytic coated vesicle formation. Current Biology, 8(25), 1399-1404. https://doi.org/10.1016/s0960-9822(98)00022-0