Lowe syndrome protein OCRL1 interacts with clathrin and regulates protein trafficking between endosomes and the trans-Golgi network

Rawshan Choudhury, Aipo Diao, Fang Zhang, Evan Eisenberg, Agnes Saint-Pol, Catrin Williams, Athanasios Konstantakopoulos, John Lucocq, Ludger Johannes, Catherine Rabouille, Lois E. Greene, Martin Lowe

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Oculocerebrorenal syndrome of Lowe is caused by mutation of OCRL1, a phosphatidylinositol 4,5-bisphosphate 5-phosphatase localized at the Golgi apparatus. The cellular role of OCRL1 is unknown, and consequently the mechanism by which loss of OCRL1 function leads to disease is ill defined. Here, we show that OCRL1 is associated with clathrin-coated transport intermediates operating between the trans-Golgi network (TGN) and endosomes. OCRL1 interacts directly with clathrin heavy chain and promotes clathrin assembly in vitro. Interaction with clathrin is not, however, required for membrane association of OCRL1. Overexpression of OCRL1 results in redistribution of clathrin and the cation-independent mannose 6-phosphate receptor (CI-MPR) to enlarged endosomal structures that are defective in retrograde trafficking to the TGN. Depletion of cellular OCRL1 also causes partial redistribution of a CI-MPR reporter to early endosomes. These findings suggest a role for OCRL1 in clathrin-mediated trafficking of proteins from endosomes to the TGN and that defects in this pathway might contribute to the Lowe syndrome phenotype. © 2005 by The American Society for Cell Biology.
    Original languageEnglish
    Pages (from-to)3467-3479
    Number of pages12
    JournalMolecular Biology of the Cell
    Volume16
    Issue number8
    DOIs
    Publication statusPublished - Aug 2005

    Fingerprint

    Dive into the research topics of 'Lowe syndrome protein OCRL1 interacts with clathrin and regulates protein trafficking between endosomes and the trans-Golgi network'. Together they form a unique fingerprint.

    Cite this