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First published online April 3, 2008
doi: 10.1242/10.1242/jcs.016709
Research Article |
1 Department of Life Science, Gwangju Institute of Science and Technology, Gwangju 500-712, South Korea
2 Department of Pathology, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA
3 Department of Neuroscience, Okayama University, Okayamashi, Japan
4 Deparment of Pathology, Chosun University, Gwangju 501-759, South Korea
5 Department of Biochemistry, Dongguk University, Gyeongju 780-714, South Korea
* Author for correspondence (e-mail: sunghoe{at}gist.ac.kr)
Accepted 24 January 2008
Dynamic membrane remodeling during intracellular trafficking is controlled by the intricate interplay between lipids and proteins. BAR domains are modules that participate in endocytic processes by binding and deforming the lipid bilayer. Sorting nexin 9 (SNX9), which functions in clathrin-mediated endocytosis, contains a BAR domain, however, the properties of this domain are not well understood. Here we show that SNX9 shares many properties with other BAR domain-containing proteins, such as amphiphysin and endophilin. SNX9 is able to deform the plasma membrane, as well as liposomes, into narrow tubules and recruit N-WASP and dynamin 2 to these tubules via its SH3 domain. SNX9-induced tubulation is antagonized by N-WASP and dynamin 2 while it is enhanced by perturbation of actin dynamics. However, SNX9 also has several unique properties. The tubulating activity requires the BAR and PX domains, as well as the low-complexity (LC) domain, which binds the Arp2/3 complex. SNX9 also binds to PtdIns(4)P-5-kinases via its PX domain and its tubulating activity is regulated by phosphoinositides. In addition, the kinase activity of PtdIns(4)P-5-kinases is stimulated by interaction with SNX9, suggesting a positive feedback interaction between SNX9 and PtdIns(4)P-5-kinases. These results suggest that SNX9 functions in the coordination of membrane remodeling and fission via interactions with actin-regulating proteins, endocytic proteins and PtdIns(4,5)P2-metabolizing enzymes.
Key words: Sorting nexin 9 (SNX9), Bin-Amphiphysin-Rvs (BAR), Membrane tubulation, Clathrin-mediated endocytosis, Neural Wiskott-Aldrich syndrome protein (N-WASP), Dynamin, Actin cytoskeleton
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