A negative feedback regulation of mTORC1 by the lysosomal Ca2+ release channel TRPML1 in cellular homeostasis and human diseases

发布时间 : 2018/07/06点击量:
报告题目:A negative feedback regulation of mTORC1 by the lysosomal Ca2+ release channel TRPML1 in cellular homeostasis and human diseases

报 告 人:Xianping Dong, Ph.D., Associate Professor

报告人单位:Department of Physiology and Biophysics, Faculty of Medicine, Dalhousie University, Canada

报告时间:2018年7月6日15:00-16:30

报告地点:金沙8888js官方一楼北厅

Research interests:
Professor Dong’s research interests include lysosome physiology and lysosome-related diseases. His primary interests are lysosomal ion channels and transporters. Investigation of these lysosomal channels and transporters will facilitate our understanding of the pathogenic mechanisms of many lysosomal storage diseases as well as neurodegenerative diseases.

Selected publications
1. Sun X, Yang Y, Zhong XZ, Cao Q, Zhu XH, Zhu X, Dong XP. A negative feedback regulation of mTORC1 activity by the lysosomal Ca2+ channel TRPML1 using a calmodulin-dependent mechanism. Autophagy, 2018;14(1):38-52.

2. Cao Q, Yang Y, Zhong XZ, Dong XP. The lysosomal Ca2+ release channel TRPML1 regulates lysosome size by activating calmodulin. J Biol Chem. 2017; 292(20):8424-8435.

3. Zhong XZ, Zou Y, Sun X, Dong G Sr, Cao Q, Pandey A, Rainey JK, Zhu X, Dong XP. Inhibition of TRPML1 by lysosomal adenosine involved in severe combined immunodeficiency diseases. J Biol Chem. 2017; 292(8):3445-3455

4. Zhong XZ, Sun X, Cao Q, Dong G, Schiffmann R, Dong XP. BK channel agonist represents a potential therapeutic approach for lysosomal storage diseases. Sci Rep. 2016; 6:33684.

5. Zhong XZ, Cao Q, Sun X, Dong XP. Activation of lysosomal P2X4 by ATP transported into lysosomes via SLC17A9 using V-ATPase generated voltage gradient as the driving force. J Physiol. 2016; 594(15):4253-66.

6. Cao Q, Zhong XZ, Zou Y, Murrell-Lagnado R, Zhu MX, and Dong XP. Calcium release through P2X4 activates calmodulin to promote endolysosomal membrane fusion. J Cell Biol, 2015; 209(6):879-94.

7. Cao Q, Zhong XZ, Zou Y, Zhang Z, Ligia T, Dong XP. BK Channels Alleviate Lysosomal Storage Diseases by Providing Positive Feedback Regulation of Lysosomal Ca2+ Release. Dev Cell, 2015; 33(4):427-41.

8. Cao Q, Zhao K, Zhong XZ, Zou Y, Yu H, Huang P, Xu TL, Dong XP. SLC17A9 Protein Functions as a Lysosomal ATP Transporter and Regulates Cell Viability. J BiolChem, 2014; 289(33):23189-99.

9. Huang P, Zou Y, Zhong XZ, Cao Q, Zhao K, Zhu MX, Murrell-Lagnado R, Dong XP. P2X4 Forms Functional ATP-activated Cation Channels on Lysosomal Membranes Regulated by Luminal pH.J BiolChem, 2014; 289(25):17658-67.

10. Dong XP*, Shen D*, Wang X*, Dawson T, Li X, Zhang Q, Cheng X, Zhang Y, Weisman L, Delling M, and Xu H. PI(3,5)P2 controls intracellular membrane traffic by direct activation of mucolipin Ca2+ release channels in the endolysosome. Nature Commun, 2010, 1: 38.

11. Dong XP, Cheng X, Mills E, Delling M, Wang F, Kurz T, Xu H. The type IV mucolipidosis-associated protein TRPML1 is an endolysosomal iron release channel. Nature, 2008, 455: 992-997.

Selected awards and honours
• Presidential Award of the Chinese Academy of Sciences (2002)
• CIHR New Investigator Salary Award (2012-2017)
• Institute of Aging's Special Recognition Awards, Institute of Aging-CIHR (2012)
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