Structural highlights
Function
[I5P2_MOUSE] Hydrolyzes phosphatidylinositol 4,5-bisphosphate (PtIns(4,5)P2) and the signaling molecule phosphatidylinositol 1,4,5-trisphosphate (PtIns(1,4,5)P3), and thereby modulates cellular signaling events.[1] [2]
Publication Abstract from PubMed
OCRL, whose mutations are responsible for Lowe syndrome and Dent disease, and INPP5B are two similar proteins comprising a central inositol 5-phosphatase domain followed by an ASH and a RhoGAP-like domain. Their divergent NH2-terminal portions remain uncharacterized. We show that the NH2-terminal region of OCRL, but not of INPP5B, binds clathrin heavy chain. OCRL, which in contrast to INPP5B visits late stage endocytic clathrin-coated pits, was earlier shown to contain another binding site for clathrin in its COOH-terminal region. NMR structure determination further reveals that despite their primary sequence dissimilarity, the NH2-terminal portions of both OCRL and INPP5B contain a PH domain. The novel clathrin-binding site in OCRL maps to an unusual clathrin-box motif located in a loop of the PH domain, whose mutations reduce recruitment efficiency of OCRL to coated pits. These findings suggest an evolutionary pressure for a specialized function of OCRL in bridging phosphoinositide metabolism to clathrin-dependent membrane trafficking.
A PH domain within OCRL bridges clathrin-mediated membrane trafficking to phosphoinositide metabolism.,Mao Y, Balkin DM, Zoncu R, Erdmann KS, Tomasini L, Hu F, Jin MM, Hodsdon ME, De Camilli P EMBO J. 2009 Jul 8;28(13):1831-42. Epub 2009 Jun 18. PMID:19536138[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ O'Malley CJ, McColl BK, Kong AM, Ellis SL, Wijayaratnam AP, Sambrook J, Mitchell CA. Mammalian inositol polyphosphate 5-phosphatase II can compensate for the absence of all three yeast Sac1-like-domain-containing 5-phosphatases. Biochem J. 2001 May 1;355(Pt 3):805-17. PMID:11311145
- ↑ Matzaris M, O'Malley CJ, Badger A, Speed CJ, Bird PI, Mitchell CA. Distinct membrane and cytosolic forms of inositol polyphosphate 5-phosphatase II. Efficient membrane localization requires two discrete domains. J Biol Chem. 1998 Apr 3;273(14):8256-67. PMID:9525932
- ↑ Mao Y, Balkin DM, Zoncu R, Erdmann KS, Tomasini L, Hu F, Jin MM, Hodsdon ME, De Camilli P. A PH domain within OCRL bridges clathrin-mediated membrane trafficking to phosphoinositide metabolism. EMBO J. 2009 Jul 8;28(13):1831-42. Epub 2009 Jun 18. PMID:19536138 doi:10.1038/emboj.2009.155
