All known patient mutations in the ASH-RhoGAP domains of OCRL affect targeting and APPL1 binding

Heather J. McCrea, Summer Paradise, Livia Tomasini, Maria Addis, Maria Antonietta Melis, Maria Antonietta De Matteis, Pietro De Camilli

Research output: Contribution to journalArticlepeer-review

49 Scopus citations


Mutations in the inositol 5-phosphatase OCRL are responsible for Lowe syndrome, an X-linked disorder characterized by bilateral cataracts, mental retardation, neonatal hypotonia, and renal Fanconi syndrome, and for Dent disease, another X-linked condition characterized by kidney reabsorption defects. We have previously described an interaction of OCRL with the endocytic adaptor APPL1 that links OCRL to protein networks involved in the disease phenotype. Here, we provide new evidence showing that among the interactions which target OCRL to membranes of the endocytic pathway, binding to APPL1 is the only one abolished by all known disease-causing missense mutations in the ASH-RhoGAP domains of the protein. Furthermore, we demonstrate that APPL1 and rab5 independently contribute to recruit OCRL to enlarged endosomes induced by the expression of constitutively active Rab5. Thus, binding to APPL1 helps localize OCRL at specific cellular sites, and disruption of this interaction may play a role in disease.

Original languageEnglish (US)
Pages (from-to)493-499
Number of pages7
JournalBiochemical and biophysical research communications
Issue number2
StatePublished - May 2 2008
Externally publishedYes


  • APPL1
  • Endosome
  • Lowe Syndrome
  • OCRL
  • Oculocerebrorenal Syndrome of Lowe
  • Rab5

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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