Role of the ENTH domain in phosphatidylinositol-4,5-bisphosphate binding and endocytosis

T. Itoh, S. Koshiba, T. Kigawa, A. Kikuchi, S. Yokoyama, T. Takenawa

Research output: Contribution to journalArticlepeer-review

373 Citations (Scopus)

Abstract

Endocytic proteins such as epsin, AP180, and Hip 1R (Sla2p) share a conserved modular region termed the epsin NH2-terminal homology (ENTH) domain, which plays a crucial role in clathrin-mediated endocytosis through an unknown target. Here, we demonstrate a strong affinity of the ENTH domain for phosphatidylinositol-4,5-bisphosphate [PtdIns(4,5)P2]. With nuclear magnetic resonance analysis of the epsin ENTH domain, we determined that a cleft formed with positively charged residues contributed to phosphoinositide binding. Overexpression of a mutant, epsin Lys76→ Ala76, with an ENTH domain defective in phosphoinositide binding, blocked epidermal growth factor internalization in COS-7 cells. Thus, interaction between the ENTH domain and PtdIns(4,5)P2 is essential for endocytosis mediated by clathrin-coated pits.

Original languageEnglish
Pages (from-to)1047-1051
Number of pages5
JournalScience
Volume291
Issue number5506
DOIs
Publication statusPublished - 2001

ASJC Scopus subject areas

  • General

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