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Synaptojanin 2 functions at an early step of clathrin-mediated endocytosis
Author(s): Rusk N, Le PU, Mariggio S, Guay G, Lurisci C, Nabi IR, Corda D, Symons M
Source: CURRENT BIOLOGY    Volume: 13    Issue: 8    Pages: 659-663    Published: APR 15 2003  
Times Cited: 26     References: 20     
Abstract: Synaptojanin 2 is a ubiquitously expressed polyphosphoinositide phosphatase that displays a high degree of homology in its catalytic domains with synaptojanin 1 [1, 2]. Neurons of synaptojanin 1-deficient mice display an increase in clathrin-coated vesicles and delayed reentry of recycling vesicles into the fusion-competent vesicle pool, but no defects in early steps of endocytosis [3, 4]. Here we show that inhibition of synaptojanin 2 expression via small interfering (si) RNA causes a strong defect in clathrin-mediated receptor internalization in a lung carcinoma cell line. This inhibitory phenotype is rescued by overexpression of wildtype synaptojanin 2, but not of wild-type synaptojanin I or mutant synaptojanin 2 that is deficient in 5'-phosphatase activity. In addition, electron-microscopic analysis shows that synaptojanin 2 depletion causes a decrease in clathrin-coated pits and vesicles. These results suggest a role for synaptojanin 2 in clathrin-coated pit formation and imply that lipid hydrolysis is required at an early stage of clathrin-mediated endocytosis. Taken together, our results also indicate that synaptojanin 2 is functionally distinct from synaptojanin 1.
Document Type: Article
Language: English
Reprint Address: Symons, M (reprint author), N Shore LIJ Res Inst, Ctr Oncol & Cell Biol, 350 Community Dr, Manhasset, NY 11030 USA
Addresses:
1. N Shore LIJ Res Inst, Ctr Oncol & Cell Biol, Manhasset, NY 11030 USA
2. Univ Montreal, Dept Pathol & Cell Biol, Montreal, PQ H3C 3J7 Canada
3. Ist Ric Farmacol Mario Negri, Consorzio Mario Negri Sud, Dept Cell Biol & Oncol, I-66030 Santa Maria Imbaro, Italy
4. N Shore LIJ Res Inst, Dept Surg, Manhasset, NY 11030 USA
5. Yeshiva Univ Albert Einstein Coll Med, Dept Surg, Bronx, NY 10461 USA
6. Yeshiva Univ Albert Einstein Coll Med, Dept Anat & Struct Biol, Bronx, NY 10461 USA
Publisher: CELL PRESS, 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA
Subject Category: Biochemistry & Molecular Biology
IDS Number: 671XG
ISSN: 0960-9822
DOI: 10.1016/S0960-9822(03)00241-0
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