Targeting of the FYVE domain to endosomal membranes is regulated by a histidine switch.

ABSTRACT: Specific recognition of phosphatidylinositol 3-phosphate [PtdIns3P] by the FYVE domain targets cytosolic proteins to endosomal membranes during key signaling and trafficking events within eukaryotic cells. Here, we show that this membrane targeting is regulated by the acidic cellular environment. Lowering the cytosolic pH enhances PtdIns3P affinity of the FYVE domain, reinforcing the anchoring of early endosome antigen 1 (EEA1) to endosomal membranes. Reversibly, increasing the pH disrupts phosphoinositide binding and leads to cytoplasmic redistribution of EEA1. pH dependency is due to a pair of conserved His residues, the successive protonation of which is required for PtdIns3P head group recognition as revealed by NMR. Substitution of the His residues abolishes PtdIns3P binding by the FY

SUBMITTER: Lee SA 

PROVIDER: S-EPMC1201587 | biostudies-literature | 2005 Sep

REPOSITORIES: biostudies-literature