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PDBsum entry 2qv2
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References listed in PDB file
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Key reference
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Title
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A role of the lowe syndrome protein ocrl in early steps of the endocytic pathway.
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Authors
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K.S.Erdmann,
Y.Mao,
H.J.Mccrea,
R.Zoncu,
S.Lee,
S.Paradise,
J.Modregger,
D.Biemesderfer,
D.Toomre,
P.De camilli.
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Ref.
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Dev Cell, 2007,
13,
377-390.
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PubMed id
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Abstract
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Mutations in the inositol 5-phosphatase OCRL are responsible for Lowe syndrome,
whose manifestations include mental retardation and renal Fanconi syndrome. OCRL
has been implicated in membrane trafficking, but disease mechanisms remain
unclear. We show that OCRL visits late-stage, endocytic clathrin-coated pits and
binds the Rab5 effector APPL1 on peripheral early endosomes. The interaction
with APPL1, which is mediated by the ASH-RhoGAP-like domains of OCRL and is
abolished by disease mutations, provides a link to protein networks implicated
in the reabsorptive function of the kidney and in the trafficking and signaling
of growth factor receptors in the brain. Crystallographic studies reveal a role
of the ASH-RhoGAP-like domains in positioning the phosphatase domain at the
membrane interface and a clathrin box protruding from the RhoGAP-like domain.
Our results support a role of OCRL in the early endocytic pathway, consistent
with the predominant localization of its preferred substrates, PI(4,5)P(2) and
PI(3,4,5)P(3), at the cell surface.
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