上海生科院最新《Nature》文章

　　

来自上海生命科学研究院的消息，中国科学院上海生命科学研究院营养科学研究所Fudi Wang博士研究组与美国密歇根大学的Haoxing Xu博士、波士顿儿童医院以及瑞典的科学家合作，首次阐明了TRPML1是一种二价铁离子(Fe2+)通道。研究成果《The type IV mucolipidosis-associated protein TRPML1 is an endolysosomal iron release channel》近期发表在《自然》杂志上。

TRPML1是TRP(transient receptor potential)离子通道蛋白，分布在细胞内体和溶酶体，在人类粘脂质累积病IV型（Mucolipidosis, ML4）患者中发现有突变。ML4是一种罕见的严重遗传性神经疾病，其主要临床表现为运动障碍、智力低下、视网膜变性和缺铁性贫血，且随着患者年龄增长症状会逐渐加重。以往研究推测，TRPML1是一种Ca2+通道，Ca2+代谢紊乱导致ML4发病。Fudi Wang博士研究组及其合作者利用多种前沿生物学技术，包括放射性铁离子吸收定量测定、金属离子特异荧光成像以及细胞内体溶酶体膜片钳揭示TRPML1实际上是Fe2+通道。在酸性条件下，正常晚期内体和溶酶体中TRPML1具有非常强的泵出Fe2+的能力；而ML4突变的TRPML1蛋白却表现为泵出Fe2+的功能受到抑制或阻断。因此，细胞内铁离子转运障碍是导致ML4发病的真正分子机理。基于TRPML1在细胞内铁代谢中的重要作用，设计针对溶酶体靶向的铁螯合物可能会成为治疗ML4患者的新举措。“TRPML1是分布在细胞内体和溶酶体的二价铁离子通道”这一重要发现不仅极大地丰富和完善了细胞铁稳态调控理论体系，而且还对铁代谢相关疾病，包括癌症、糖尿病、神经退行性病变等的预防和治疗的研究开辟了新的途径。

Fudi Wang研究组重点研究微量元素锌和铁的稳态调控机理，并通过多种生物学技术和实验体系筛选和鉴定新的金属离子转运相关基因。TRPML1是继Mon1a（Nature Genetics， 2007）和Sec15L1 （Nature Genetics， 2005）之后Fudi Wang博士独立或参与发现的第三个铁代谢调控新基因。目前，该研究组正与多家科研单位合作，继续对TRPML1导致ML4的分子机理进行深入研究。

附：
Fudi Wang

Ph.D., Professor
Principal Investigator

Email: [e-mail]

Dr. Wang earned his Bachelor's degree from the School of Public Health at HeBei Medical University in 1992, obtained his Master's degree from the School of Medicine at Shanghai Tongji University in 1995, and received his Ph.D. from the Department of Public Health at Second Military Medical University in 1998. He first worked as an Assistant Professor and then Associate Professor and Department Chair in the Faculty of Naval Medicine, Second Military Medical University from 1998 to 2002. Dr. Wang completed postdoctoral training in the Department of Nutritional Sciences and Biochemistry, University of Missouri-Columbia from 2002 to 2004. He served as an Instructor at Harvard Medical School and Children's Hospital Boston from 2004 to 2008. Dr. Wang joined the faculty of the Institute for Nutritional Sciences at Shanghai, China in 2008.

RESEARCH INTERESTS:
My laboratory is interested in investigating molecular mechanisms of zinc and iron metabolism by applying molecular, cell biological, biochemical, and genetic approaches. Our current studies focus on ZIP zinc transporters, erythroid iron metabolism, macrophages iron recycling and the novel iron modifier proteins.