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Phosphatidylinositol-4,5-bisphosphate is required for endocytic coated vesicle formation
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.
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“It has been well established that PIP2, the predominant PI formed at the plasma membrane, is required for clathrin-mediated endocytosis, with roles in clathrin-coated pit initiation, stabilization, and maturation14-17.”
From Transmembrane Protein 55B Is a Novel Regulator of Cellular Cholesterol Metabolism (2014) · cites this paper as [14]
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Cites
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Metadata
- Authors
- Jost, M., Simpson, F., Kavran, J. M., Lemmon, M. A., & Schmid, S. L.
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 1998-12
- Volume
- 8
- Issue
- 25
- Pages
- 1399-1404
- ISSN
- 0960-9822
- Cited by
- 227
- References
- 1
- Language
- en
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 5342 d)
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