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J. Biol. Chem., Vol. 281, Issue 48, 36891-36896, December 1, 2006

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Sorting Nexin 10 Induces Giant Vacuoles in Mammalian Cells^*

From the Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510663, China

Eukaryotic cells maintain a sophisticated network of intracellular membranous system to ensure the proper distribution and compartmentalization of cellular proteins critical for diverse functions such as cell division or cell-cell communication. Yet, little is known about the mechanism that regulates the homeostasis of this system. While analyzing the impact of sorting nexins on the trafficking of membrane type matrix metalloproteinases, we unexpectedly discovered that the expression of SNX10 induced the formation of giant vacuoles in mammalian cells. This vacuolizing activity is sensitive to mutations at the putative phosphoinositide 3-phosphate binding residue Arg⁵³. Domain-swap experiments with SNX3 demonstrate that the PX domain of SNX10 alone is insufficient to generate vacuoles and the downstream C-terminal domain is required for vacuolization. Brefeldin A, a chemical known to block the endoplasmic reticulum to Golgi transport, inhibited the vacuolization process. Together, these results suggest that SNX10 activity may be involved in the regulation of endosome homeostasis.

Received for publication, September 15, 2006

^* This work was supported in part by the Guangzhou Institute for Biomedicine and Health funds provided by the Chinese Academy of Sciences, Science and Technology divisions of Guangdong and Guangzhou. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed. E-mail: pei_duanqing{at}gibh.ac.cn.

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