李洪生最新Cell文章解析GPCR新发现

　　

生物通报道：来自美国麻州大学医学院（University of Massachusetts Medical School）神经生物学系的研究人员分离得到了两个光电响应（photoresponse）慢终止（slow termination）的非补足（noncomplementary）果蝇突变，这些突变揭示了一种视觉G蛋白耦联受体（G protein-coupled receptor，GPCR）：视紫质失活的突变情况，为研究Ca²⁺刺激的GPCRs活性调控提供了重要资料。这一研究成果公布在11月17日《Cell》杂志上。

 

 

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相关链接：

GPCRs之功能基因组研究

Cell文章GPCR信号途径研究的最新进展

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领导这一研究的是来自麻州大学医学院的李洪生（Hong-Sheng Li，音译）博士，他早年毕业于武汉大学生命科学学院生化与生物物理学系，在中科院上海脑研究所获得博士学位。

链接：
Cell, Vol 127, 847-858, 17 November 2006
The Fly CAMTA Transcription Factor Potentiates Deactivation of Rhodopsin, a G Protein-Coupled Light Receptor
[Abstract]

人类细胞在与营养物质、毒素、激素甚至光线反应时，必须能够发送启动或关闭生命过程的信号。而GPCRs就是这类信号级联（如传递视觉信号、携带神经信息、使白血球工具感染并设置心跳的时间节律等）的一个关键部分。此外，GPCR信号还在多种重要疾病中扮演关键的角色。因此，GCPR已经成为20种最畅销药物中的12种药物的作用靶标，这些药物包括充血性心力衰竭药物Coreg、高血压药物Cozaar、乳腺癌药物Zoladex、焦虑药物Buspar、精神分裂药物Clozaril。此外，Zantac和Claritin的作用靶标也是GPCR。这类药物每年的销售总额高达2000亿美元。

在这篇研究中主要针对的是膜受体活性在保护细胞免受兴奋毒素（excitotoxicity）毒害的作用。研究人员通过遗传学和电生理学方法对其分离得到的两个非补足性果蝇突变进行分析，发现这是一种视紫质G蛋白耦联受体失活缺陷形式，最后这一突变基因被辨认为钙调素结合转录激活因子（calmodulin-binding transcription activator ，dCAMTA)。目前已知视紫质调控因子Arr2并没有介导这个dCAMTA视觉功能过程，研究人员通过全基因组筛选发现了5个dCAMTA靶标基因，其中F box基因：dFbxl4的过量表达可以逆转这些突变表型。研究人员进一步的研究也发现体内dCAMTA通过与Ca²⁺传感钙调素相互作用可以刺激表达。这些研究成果都说明了calmodulin/CAMTA/Fbxl4也许在Ca²⁺刺激GPCRs的活性长时程反馈调控中起作用，并阻止由于多余Ca²⁺流入引起的细胞伤害。

附：
Hong-Sheng Li, Ph.D.
Assistant Professor

Address Departments of Neurobiology
University of Massachusetts Medical School
364 Plantation St., LRB 722
Worcester, MA 01655

Telephone [phone] Fax [phone]

Email [e-mail]; [e-mail]

Birth July 16, 1969, Xiantao, Hubei, P. R. China


Education 

Ph.D. 1991-96 Shanghai Brain Research Institute,
Chinese Academy of Sciences, Shanghai 200031, China

B. S. 1987-91 Department of Biochemistry and Biophysics, School of Life Sciences,
Wuhan University, Wuhan, Hubei 430072, China

Research Experience

2002-present Assistant Professor, Univ. Mass. Medical School, Dept. Neurobiol., Worcester
Regulation of TRP calcium channels in Drosophila and mammals

1996-2001 Postdoctoral fellow, the Johns Hopkins University School of Medicin, Baltimore
Phototransduction in Drosophila retina
Functional analysis of vertebrate TRPC calcium channels
Advisor: Dr. Craig Montell

1991-1996 Graduate student, Shanghai Brain Research Institute, Shanghai
The roles of tachykinin receptors in primary nociception 
Effects of cholecystokinin on trigeminal sensory neurons
Advisor: Dr. Zhi-Qi Zhao


Memberships:

1. The Society for Neuroscience.

2. The International Brain Research Organization (IBRO).

Honors

2001 The Albert L. Lehninger Postdoctoral Fellow Award, Johns Hopkins University

1998 The Chinese Academy of Science Natural Science Achievement Award, Beijing

The Outstanding Young Scientist Award in the first biennial meeting of the Chinese Society for Neuroscience

1995 BECKMAN Outstanding Young Scientist Award, Shanghai

Research Support

08/01/03-07/31/08 NIH R01 AG022508 (Principle Investigator)
Functional Analysis of the dCAMTA Transcription Factor

Selected Peer-reviewed Publications

Li HS and Zhao ZQ (1994). Progress in the study of molecular neurobiology of substance P. Sheng Li Ko Hsueh Chin Chan (Progress in Physiological Sciences) 25(1) 31-47. (Review in Chinese)

Duan SM, Li HS and Zhao ZQ (1996). Effects of cholecystokinin in spinal trigeminal nucleus caudalis neurons in vitro. Chinese Science Bulletin 41(21) 1827-1830.

Xu XZ, Li HS (equal contributors), Guggino WB and Montell C (1997). Coassembly of TRP and TRPL produces a distinct store-operated conductance. Cell 89(7) 1155-64.

Li HS and Zhao ZQ (1998). Small sensory neurons in the rat dorsal root ganglia express functional NK-1 tachykinin receptor. Eur. J. Neurosci. 10(4) 1292-1299.

Li HS, Bao YD and Zhao ZQ (1998). Expression of tachykinin receptors in Xenopus oocytes injected with poly(A)+ RNA from cat dorsal root ganglion. Science in China series C 41(2) 139-145.

Li HS, Porter JA and Montell C (1998). Requirement for the NINAC kinase/myosin for stable termination of the visual cascade. J. Neurosci. 18(23) 9601-9606.

Xu XZS, Wes PD, Chen H, Li HS, Yu M, Morgan S, Liu Y and Montell C (1998). Retinal targets for calmodulin include proteins implicated in synaptic transmission. J. Biol. Chem. 273(47) 31297-31307. 

Li HS, Xu XZS, and Montell C (1999). Activation of a TRPC3-dependent cation current through the neurotrophin, BDNF. Neuron 24(1) 261-273.

Wes PD, Xu XZS, Li HS, Chien F, Doberstein SK, and Montell C (1999). Interaction between the unconventional myosin, NINAC, and the PDZ domain protein, INAD, is essential for termination of phototransduction. Nature Neurosci. 2(5) 447-453. 

Li HS and Montell C (2000). TRP and the PDZ Protein, INAD, form the core complex required for retention of the signalplex in Drosophila photoreceptor cells. J. Cell Biol. 150(6) 1411-1421.

Ma HT, Venkatachalam K, Li HS, Montell C, Kurosaki T, Patterson RL, and Gill DL (2001). Assessment of the role of the InsP3 receptor in the activation of TRP channels and store-operated Ca2+ entry channels. J. Biol. Chem. 276(22) 18888-18896.

Xu H, Lee SJ, Suzuki E, Dugan KD, Stoddard A, Li HS, Chodosh LA and Montell C (2004). A lysosomal tetraspanin associated with retinal degeneration identified via a genome-wide screen. EMBO J. 23(4) 811-822.

Conference Presentations:

Formalin-induced inflammation increases the number of neurons transcripting tachykinin receptor mRNAs in the superficial dorsal horn of the rat spinal cord. The Fourth IBRO World Congress of Neurosciences. July 1995, Kyoto.

Calmodulin binding proteins in the Drosophila retina. Meeting on Neurobiology of Drosophila. September 1997, New York.

Association of the TRP and TRPL store-operated Ca2+ channels with a supramolecular signaling complex. Meeting on Neurobiology of Drosophila. September 1997, New York.

TRPC3, a vertebrate homolog of the Drosophila light-stimulated TRP channel, is a downstream effector of the neurotrophin receptor TrkB. The 29th Annual Meeting of the Society for Neuroscience. October 1999, Miami Beach.
（生物通：万纹）