细胞囊泡运输发现者获诺贝尔生理学或医学奖

　　诺贝尔奖官网消息，2013年诺贝尔生理学或医学奖7日下午揭晓，耶鲁大学教授詹姆斯-E.罗斯曼、加州大学伯克利分校教授兰迪-W.谢克曼及 德国生物化学家托马斯-C.苏德霍夫因在细胞内主要运输系统的新发现而获奖。诺奖委员会说，三人发现了细胞内囊泡交通的运行与调节机制。此前呼声很高的细胞自噬和甲基化（表观遗传学）未能在今年获奖。

　　生物体内每一个细胞都是一个生产和运输分子的工厂。比如，胰岛素在这里被制造出来并释放进入血液当中，以及神经传递素从一个神经细胞传导至另一 个细胞。这些分子在细胞内都是以“小包”的形式传递的，即细胞囊泡。这三位获奖科学家发现了这些“小包”是如何被在正确的时间输运至正确地点的分子机制。

　　兰迪-W.谢克曼发现了一系列与细胞囊泡输运机制有关的基因。詹姆斯-E.罗斯曼则发现了让这些囊泡得以与其目标相融合的蛋白质机制，从而可以实现对所运“货物”的传递。托马斯-C.苏德霍夫则揭示了信号是如何实现对囊泡的控制，使其得以精确分配其所载“货物”。

　　在这项发现过程中，三位科学家：罗斯曼， 谢克曼和苏德霍夫揭示了细胞内输运体系的精细结构和控制机制。这一系统的失稳将导致有害结果，如神经系统疾病，糖尿病或免疫系统紊乱。

　　获奖者简介：

　　詹姆斯-E.罗斯曼

　　1947年出生(66岁)，耶鲁大学细胞生物学系系主任、纪念Fergus F. Wallace生物医学教授。曾获多种荣誉，包括哥伦比亚大学的露依莎-格罗斯-霍维茨奖、拉斯克奖基础医学奖(2002年)、费萨尔国王奖。

　　兰迪-W.谢克曼

　　1948年出生(65岁)，加州大学伯克利分校细胞生物学家，曾任《美国国家科学院院刊》主编。1992年当选美国国家科学院院士。2002年与詹姆斯-罗思曼因对细胞膜传输的研究获拉斯克基础医学奖。

　　托马斯-C.苏德霍夫

　　1955年出生(58岁)，德国生物化学家，以研究突触传递知名。自1986年以来聚德霍夫博士的研究已经阐明了许多主要的蛋白介导突触前功能。2013年和理查德-舍勒分享了拉斯克基础医学奖。

诺贝尔得主的主要文献，从文章来看，三位得奖者也曾有过密切合作：

James E. Rothman代表性文章

Gao Y, Zorman S, Gundersen G, Xi Z, Ma L, Sirinakis G, Rothman JE, Zhang Y.Single reconstituted neuronal SNARE complexes zipper in three distinct stages.Science. 2012 Sep 14;337(6100):1340-3.

Shi L, Shen QT, Kiel A, Wang J, Wang HW, Melia TJ, Rothman JE, Pincet F.SNARE proteins: one to fuse and three to keep the nascent fusion pore open.Science. 2012 Mar 16;335(6074):1355-9.

Südhof TC, Rothman JE.Membrane fusion: grappling with SNARE and SM proteins.Science. 2009 Jan 23;323(5913):474-7.

Shen J, Tareste DC, Paumet F, Rothman JE, Melia TJ.Selective activation of cognate SNAREpins by Sec1/Munc18 proteins.Cell. 2007 Jan 12;128(1):183-95

Giraudo CG, Eng WS, Melia TJ, Rothman JE.A clamping mechanism involved in SNARE-dependent exocytosis.Science. 2006 Aug 4;313(5787):676-80

Burri L, Varlamov O, Doege CA, Hofmann K, Beilharz T, Rothman JE, Söllner TH, Lithgow T. A SNARE required for retrograde transport to the endoplasmic reticulum.Proc Natl Acad Sci U S A. 2003 Aug 19;100(17):9873-7

Hu C, Ahmed M, Melia TJ, Söllner TH, Mayer T, Rothman JE. Fusion of cells by flipped SNAREs.Science. 2003 Jun 13;300(5626):1745-9

Rothman JE.Lasker Basic Medical Research Award. The machinery and principles of vesicle transport in the cell. Nat Med. 2002 Oct;8(10):1059-62

Parlati F, Varlamov O, Paz K, McNew JA, Hurtado D, Söllner TH, Rothman JE.Distinct SNARE complexes mediating membrane fusion in Golgi transport based on combinatorial specificity.Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5424-9

Randy W. Schekman 主要代表性文章
Schekman RW.Retrospective: George E. Palade (1912-2008). Science. 2008 Oct 31;322(5902):695.

Kim J, Kleizen B, Choy R, Thinakaran G, Sisodia SS, Schekman RW.Biogenesis of gamma-secretase early in the secretory pathway. J Cell Biol. 2007 Dec 3;179(5):951-63

Valdivia RH, Baggott D, Chuang JS, Schekman RW.The yeast clathrin adaptor protein complex 1 is required for the efficient retention of a subset of late Golgi membrane proteins. Dev Cell. 2002 Mar;2(3):283-94

Thomas C. Südhof  主要代表性文章(仅Cell, Nature, Science上文章就接近30篇）

Aoto J, Martinelli DC, Malenka RC, Tabuchi K, Südhof TC.Presynaptic neurexin-3 alternative splicing trans-synaptically controls postsynaptic AMPA receptor trafficking.Cell. 2013 Jul 3;154(1):75-88.

Burré J, Vivona S, Diao J, Sharma M, Brunger AT, Südhof TC.Properties of native brain α-synuclein.Nature. 2013 Jun 13;498(7453):E4-6; discussion E6-7.

Xu W, Südhof TC.A neural circuit for memory specificity and generalization.Science. 2013 Mar 15;339(6125):1290-5.

Rizo J, Südhof TC.The membrane fusion enigma: SNAREs, Sec1/Munc18 proteins, and their accomplices--guilty as charged?Annu Rev Cell Dev Biol. 2012;28:279-308.

Pang ZP, Yang N, Vierbuchen T, Ostermeier A, Fuentes DR, Yang TQ, Citri A, Sebastiano V, Marro S, Südhof TC, Wernig M.Induction of human neuronal cells by defined transcription factors.Nature. 2011 May 26;476(7359):220-3.

Cao P, Maximov A, Südhof TC.Activity-dependent IGF-1 exocytosis is controlled by the Ca(2+)-sensor synaptotagmin-10.Cell. 2011 Apr 15;145(2):300-11.

Kaeser PS, Deng L, Wang Y, Dulubova I, Liu X, Rizo J, Südhof TC.RIM proteins tether Ca2+ channels to presynaptic active zones via a direct PDZ-domain interaction. Cell. 2011 Jan 21;144(2):282-95.

Burré J, Sharma M, Tsetsenis T, Buchman V, Etherton MR, Südhof TC.Alpha-synuclein promotes SNARE-complex assembly in vivo and in vitro.Science. 2010 Sep 24;329(5999):1663-7.

Vierbuchen T, Ostermeier A, Pang ZP, Kokubu Y, Südhof TC, Wernig M.Direct conversion of fibroblasts to functional neurons by defined factors.Nature. 2010 Feb 25;463(7284):1035-41
 
Zhang C, Wu B, Beglopoulos V, Wines-Samuelson M, Zhang D, Dragatsis I, Südhof TC, Shen J.Presenilins are essential for regulating neurotransmitter release.Nature. 2009 Jul 30;460(7255):632-6.

Maximov A, Tang J, Yang X, Pang ZP, Südhof TC.Complexin controls the force transfer from SNARE complexes to membranes in fusion.Science. 2009 Jan 23;323(5913):516-21.

Südhof TC, Rothman JE.Membrane fusion: grappling with SNARE and SM proteins.Science. 2009 Jan 23;323(5913):474-7.

Südhof TC.Neuroligins and neurexins link synaptic function to cognitive disease.Nature. 2008 Oct 16;455(7215):903-11.

Gerber SH, Rah JC, Min SW, Liu X, de Wit H, Dulubova I, Meyer AC, Rizo J, Arancillo M, Hammer RE, Verhage M, Rosenmund C, Südhof TC.Conformational switch of syntaxin-1 controls synaptic vesicle fusion.Science. 2008 Sep 12;321(5895):1507-10.

Mukherjee K, Sharma M, Urlaub H, Bourenkov GP, Jahn R, Südhof TC, Wahl MC.CASK Functions as a Mg2+-independent neurexin kinase.Cell. 2008 Apr 18;133(2):328-39

Sun J, Pang ZP, Qin D, Fahim AT, Adachi R, Südhof TC.A dual-Ca2+-sensor model for neurotransmitter release in a central synapse.Nature. 2007 Nov 29;450(7170):676-82

Tabuchi K, Blundell J, Etherton MR, Hammer RE, Liu X, Powell CM, Südhof TC.A neuroligin-3 mutation implicated in autism increases inhibitory synaptic transmission in mice. Science. 2007 Oct 5;318(5847):71-6

Südhof TC.Synaptic vesicles: an organelle comes of age.Cell. 2006 Nov 17;127(4):671-3.

Tang J, Maximov A, Shin OH, Dai H, Rizo J, Südhof TC.A complexin/synaptotagmin 1 switch controls fast synaptic vesicle exocytosis.Cell. 2006 Sep 22;126(6):1175-87.

Chandra S, Gallardo G, Fernández-Chacón R, Schlüter OM, Südhof TC. Alpha-synuclein cooperates with CSPalpha in preventing neurodegeneration.Cell. 2005 Nov 4;123(3):383-96

Sudhof TC.The synaptic vesicle cycle.Annu Rev Neurosci. 2004;27:509-47.

Lonart G, Schoch S, Kaeser PS, Larkin CJ, Südhof TC, Linden DJ.Phosphorylation of RIM1alpha by PKA triggers presynaptic long-term potentiation at cerebellar parallel fiber synapses.Cell. 2003 Oct 3;115(1):49-60

Missler M, Zhang W, Rohlmann A, Kattenstroth G, Hammer RE, Gottmann K, Südhof TC.Alpha-neurexins couple Ca2+ channels to synaptic vesicle exocytosis.Nature. 2003 Jun 26;423(6943):939-48

Jahn R, Lang T, Südhof TC.Membrane fusion.Cell. 2003 Feb 21;112(4):519-33.

Biederer T, Sara Y, Mozhayeva M, Atasoy D, Liu X, Kavalali ET, Südhof TC.SynCAM, a synaptic adhesion molecule that drives synapse assembly.Science. 2002 Aug 30;297(5586):1525-31 Castillo PE, Schoch S, Schmitz F, Südhof TC, Malenka RC.RIM1alpha is required for presynaptic long-term potentiation.Nature. 2002 Jan 17;415(6869):327-30.

Rhee JS, Betz A, Pyott S, Reim K, Varoqueaux F, Augustin I, Hesse D, Südhof TC, Takahashi M, Rosenmund C, Brose N. Beta phorbol ester- and diacylglycerol-induced augmentation of transmitter release is mediated by Munc13s and not by PKCs.Cell. 2002 Jan 11;108(1):121-33

Schoch S, Castillo PE, Jo T, Mukherjee K, Geppert M, Wang Y, Schmitz F, Malenka RC, Südhof TC. RIM1alpha forms a protein scaffold for regulating neurotransmitter release at the active zone.Nature. 2002 Jan 17;415(6869):321-6