基本信息
胡俊杰  男  博导  中国科学院生物物理研究所
电子邮件: huj@ibp.ac.cn
通信地址: 北京市朝阳区大屯路15号生物物理研究所
邮政编码: 100101

研究领域

     本实验室主要研究内质网等重要细胞器的形态与功能。内质网是一个广泛连续的膜网络,承担了蛋白合成、脂类合成和钙存储等重要功能。内质网的形态主要包括片状和管状,然而这些不同形态的膜结构如何在同一膜系统内形成,我们还知之甚少。前期研究发现一组膜蛋白reticulons和DP1/Yop1p参与了管状内质网的成形,这些膜蛋白只在管状内质网中存在,他们的过表达和敲除都会影响内质网的形态。我们纯化了两个成管膜蛋白,并发现他们在体外与脂肪重组后能形成管状膜结构。我们最近又发现嵌膜GTP酶atlastin等参与了内质网管状网络的形成,这些蛋白的缺失或突变导致内质网分叉减少,也能引起遗传性痉挛性截瘫。我们还通过结构解析等实验手段,剖析了atlastin介导膜融合的可能机制。总体来说,我们将采用细胞生物学,生物化学及结构生物学等多种方法深入研究内质网塑形和重装的分子机制,内质网的形态与功能的关联,以及与内质网功能相关的疾病。

教授课程

细胞生物学实验
膜生物学
细胞生物学
细胞信号转导

发表论文

2023

Oligomeric scaffolding for curvature generation by ER tubule-forming proteins.

Xiang Y, Lyu R, Hu J.

Nat Commun. 2023 May 5;14(1):2617. 

PMID: 37147312


Molecular basis of Climp63-mediated ER lumen spacing.

Xu L, Xiang Y, Hu J.

J Cell Sci. 2023 May 1;136(9):jcs260976.

PMID: 37039099


Small molecule agonist of mitochondrial fusion repairs mitochondrial dysfunction.

Guo Y, Zhang H, Yan C, Shen B, Zhang Y, Guo X, Sun S, Yu F, Yan J, Liu R, Zhang Q, Zhang D, Liu H, Liu Y, Zhang Y, Li W, Qin J, Lv H, Wang Z, Yuan Y, Yang JF, Zhong YT, Gao S, Zhou B, Liu L, Kong D, Hao X, Hu J, Chen Q.

Nat Chem Biol. 2023 Apr;19(4):468-477.

PMID: 36635564



2022

A SURF4 -to-proteoglycan  relay mechanism that mediates the sorting and secretion of a tagged variant of sonic hedgehog.

Tang X, Chen R, Mesias VSD,Wang T,Wang Y,Poljak K,Fan X,Miao X,Hu J,Zhang L,Huang J,Yao S,Miller EA,Guo Y.

Proc Natl Acad Sci U S A.2022 Mar

PMID: 35271396


Reconstitution of Fusion-Competent Human Placental Fusogen Syncytin-2.

Xu L, Sun S.

J Membr Biol. 2022 May 20.

PMID: 35596004


SARS-CoV-2 ORF8 reshapes the ER through forming mixed disulfides with ER oxidoreductases.

Liu P, Wang X, Sun Y, Zhao H, Cheng F, Wang J, Yang F, Hu J, Zhang H, Wang CC, Wang L.

Redox Biol. 2022 Aug;54:102388.

PMID: 35792438


DeepContact: High-throughput quantification of membrane contact sites based on electron microscopy imaging.

Liu L, Yang S, Liu Y, Li X, Hu J, Xiao L, Xu T.

J Cell Biol. 2022 Sep 5;221(9):e202106190. 

PMID: 35929833



2021

Endoplasmic reticulum composition and form: Proteins in and out.

Sun S, Tang X, Guo Y, Hu J.

Curr Opin Cell Biol. 2021 Feb 18;71:1-6.

PMID: 33611096 Review.


FIT2 organizes lipid droplet biogenesis with ER tubule-forming proteins and septins.

Chen F, Yan B, Ren J, Lyu R, Wu Y, Guo Y, Li D, Zhang H, Hu J.

J Cell Biol. 2021 May 3;220(5):e201907183.

PMID: 33861319


Atlastin 2/3 regulate ER targeting of the ULK1 complex to initiate autophagy.

Liu N, Zhao H, Zhao YG, Hu J, Zhang H.

J Cell Biol. 2021 Jul 5;220(7):e202012091. doi: 10.1083/jcb.202012091.

PMID: 33988678


Coupling and Uncoupling: Dynamic Control of Membrane Contacts.

Zhang D, Saheki Y, Kornmann B, Hu J

Front Cell Dev Biol. E-Book


SNX27-FERM-SNX1 complex structure rationalizes divergent trafficking pathways by SNX17 and SNX27.

Yong X, Zhao L, Hu W, Sun Q, Ham H, Liu Z, Ren J, Zhang Z, Zhou Y, Yang Q, Mo X, Hu J, Billadeau DD, Jia D.

Proc Natl Acad Sci U S A. 2021 Sep 7;118(36):e2105510118. doi: 10.1073/pnas.2105510118.

PMID: 34462354



2020

Structural analysis of a trimeric assembly of the mitochondrial dynamin-like GTPase Mgm1.

Yan L, Qi Y, Ricketson D, Li L, Subramanian K, Zhao J, Yu C, Wu L, Sarsam R, Wong M, Lou Z, Rao Z, Nunnari J, Hu J.

Proc Natl Acad Sci U S A. 2020 Feb 25;117(8):4061-4070.

PMID: 32041880


STIM1 interacts with termini of Orai channels in a sequential manner.

Niu L, Wu F, Li K, Li J, Zhang SL, Hu J, Wang Q.

J Cell Sci. 2020 Feb 27:jcs.239491.

PMID: 32107289


Structural insights into G domain dimerization and pathogenic mutation of OPA1.

Yu C, Zhao J, Yan L, Qi Y, Guo X, Lou Z, Hu J, Rao Z.

J Cell Biol. 2020 Jul 6;219(7):e201907098.

PMID: 32379273


A Plasmodium homolog of ER tubule-forming proteins is required for parasite virulence.

Shi X, Hai L, Govindasamy K, Gao J, Coppens I, Hu J, Wang Q, Bhanot P.

Mol Microbiol. 2020 May 20.

PMID: 32432369

 

Self-Association of Purified Reconstituted ER Luminal Spacer Climp63

Zhao J and Hu J.

Front Cell Dev Biol. 2020 June 16.

PMID: 32612999


“At last in” the physiological roles of the tubular ER network

Lv L, Niu L, Hu J.

Biophys Rep. 2020;6(4): 105-114.

Review.


Mitochondrial Fusion: The Machineries In and Out.

Gao S, Hu J.

Trends Cell Biol. 2021 Jan;31(1):62-74. 

PMID: 33092941 Review.



2019

Atlastin-1 regulates morphology and function of endoplasmic reticulum in dendrites.

Liu X, Guo X, Niu L, Li X, Sun F, Hu J, Wang X, Shen K.

Nat Commun. 2019 Feb 4;10(1):568.

PMID: 30718476

 

Atlastin-mediated membrane tethering is critical for cargo mobility and exit from the endoplasmic reticulum.

Niu L, Ma T, Yang F, Yan B, Tang X, Yin H, Wu Q, Huang Y, Yao ZP, Wang J, Guo Y, Hu J.

Proc Natl Acad Sci U S A. 2019 Jul 9;116(28):14029-14038.

PMID: 31239341

 

Structural insights of human mitofusin-2 into mitochondrial fusion and CMT2A onset.

Li YJ, Cao YL, Feng JX, Qi Y, Meng S, Yang JF, Zhong YT, Kang S, Chen X, Lan L, Luo L, Yu B, Chen S, Chan DC, Hu J, Gao S.

Nat Commun. 2019 Oct 29;10(1):4914.

PMID: 31664033 

 

Mycobacterial dynamin-like protein IniA mediates membrane fission.

Wang M, Guo X, Yang X, Zhang B, Ren J, Liu A, Ran Y, Yan B, Chen F, Guddat LW, Hu J, Li J, Rao Z.

Nat Commun. 2019 Aug 29;10(1):3906.

PMID: 31467269

 

Reciprocal regulation between lunapark and atlastin facilitates ER three-way junction formation.

Zhou X, He Y, Huang X, Guo Y, Li D, Hu J.

Protein Cell. 2019 Jul;10(7):510-525.

PMID: 30498943 

 

Calumenin-1 Interacts with Climp63 to Cooperatively Determine the Luminal Width and Distribution of Endoplasmic Reticulum Sheets.

Shen B, Zheng P, Qian N, Chen Q, Zhou X, Hu J, Chen J, Teng J.

iScience. 2019 Dec 20;22:70-80.

PMID: 31751826


2018

Visualizing Intracellular Organelle and Cytoskeletal Interactions at Nanoscale Resolution on Millisecond Timescales.

Guo Y, Li D, Zhang S, Yang Y, Liu JJ, Wang X, Liu C, Milkie DE, Moore RP, Tulu US, Kiehart DP, Hu J, Lippincott-Schwartz J, Betzig E, Li D.

Cell. 2018 Nov 15;175(5):1430-1442.e17.

PMID: 30454650 

 

LEM4 confers tamoxifen resistance to breast cancer cells by activating cyclin D-CDK4/6-Rb and ERα pathway.

Gao A, Sun T, Ma G, Cao J, Hu Q, Chen L, Wang Y, Wang Q, Sun J, Wu R, Wu Q, Zhou J, Liu L, Hu J, Dong JT, Zhu Z.

Nat Commun. 2018 Oct 9;9(1):4180.

PMID: 30301939

 

DNA damage triggers tubular endoplasmic reticulum extension to promote apoptosis by facilitating ER-mitochondria signaling.

Zheng P, Chen Q, Tian X, Qian N, Chai P, Liu B, Hu J, Blackstone C, Zhu D, Teng J, Chen J.

Cell Res. 2018 Aug;28(8):833-854.

PMID: 30030520

 

Structural basis for GTP hydrolysis and conformational change of MFN1 in mediating membrane fusion.

Yan L, Qi Y, Huang X, Yu C, Lan L, Guo X, Rao Z, Hu J, Lou Z.

Nat Struct Mol Biol. 2018 Mar;25(3):233-243.

PMID: 29483649

 

Transmembrane E3 ligase RNF183 mediates ER stress-induced apoptosis by degrading Bcl-xL.

Wu Y, Li X, Jia J, Zhang Y, Li J, Zhu Z, Wang H, Tang J, Hu J.

Proc Natl Acad Sci U S A. 2018 Mar 20;115(12):E2762-E2771.

PMID: 29507230

 

Structural basis for neutralization of Japanese encephalitis virus by two potent therapeutic antibodies.

Qiu X, Lei Y, Yang P, Gao Q, Wang N, Cao L, Yuan S, Huang X, Deng Y, Ma W, Ding T, Zhang F, Wu X, Hu J, Liu SL, Qin C, Wang X, Xu Z, Rao Z.

Nat Microbiol. 2018 Mar;3(3):287-294.

PMID: 29379207

 

Sec61β facilitates the maintenance of endoplasmic reticulum homeostasis by associating microtubules.

Zhu Y, Zhang G, Lin S, Shi J, Zhang H, Hu J.

Protein Cell. 2018 Jul;9(7):616-628.

PMID: 29168059


2017

Sequences flanking the transmembrane segments facilitate mitochondrial localization and membrane fusion by mitofusin.

Huang X, Zhou X, Hu X, Joshi AS, Guo X, Zhu Y, Chen Q, Prinz WA, Hu J.

Proc Natl Acad Sci U S A. 2017 Nov 14;114(46):E9863-E9872.

PMID: 29093165 

 

Quantitative proteomics reveal proteins enriched in tubular endoplasmic reticulum of Saccharomyces cerevisiae.

Wang X, Li S, Wang H, Shui W, Hu J.

Elife. 2017 Mar 13;6:e23816.

PMID: 28287394

 

Atlastin regulates store-operated calcium entry for nerve growth factor-induced neurite outgrowth.

Li J, Yan B, Si H, Peng X, Zhang SL, Hu J.

Sci Rep. 2017 Feb 27;7:43490.

PMID: 28240257


2016

The Vici Syndrome Protein EPG5 Is a Rab7 Effector that Determines the Fusion Specificity of Autophagosomes with Late Endosomes/Lysosomes.

Wang Z, Miao G, Xue X, Guo X, Yuan C, Wang Z, Zhang G, Chen Y, Feng D, Hu J, Zhang H.

Mol Cell. 2016 Sep 1;63(5):781-95.

PMID: 27588602 

 

Fusion of the endoplasmic reticulum by membrane-bound GTPases.

Hu J, Rapoport TA.

Semin Cell Dev Biol. 2016 Dec;60:105-111.

PMID: 27269373 Review.

 

Shaping the Endoplasmic Reticulum into a Social Network.

Zhang H, Hu J.

Trends Cell Biol. 2016 Dec;26(12):934-943.

PMID: 27339937 Review.

 

Identification of endoplasmic reticulum-shaping proteins in Plasmodium parasites.

Sun S, Lv L, Yao Z, Bhanot P, Hu J, Wang Q.

Protein Cell. 2016 Aug;7(8):615-20.

PMID: 27484902 

 

A Comprehensive Analysis of Plasmodium Circumsporozoite Protein Binding to Hepatocytes.

Zhao J, Bhanot P, Hu J, Wang Q.

PLoS One. 2016 Aug 25;11(8):e0161607.

PMID: 27560376

 

A family of membrane-shaping proteins at ER subdomains regulates pre-peroxisomal vesicle biogenesis.

Joshi AS, Huang X, Choudhary V, Levine TP, Hu J, Prinz WA.

J Cell Biol. 2016 Nov 21;215(4):515-529.

PMID: 27872254

 

Structures of human mitofusin 1 provide insight into mitochondrial tethering.

Qi Y, Yan L, Yu C, Guo X, Zhou X, Hu X, Huang X, Rao Z, Lou Z, Hu J.

J Cell Biol. 2016 Dec 5;215(5):621-629.

PMID: 27920125 


2015

Junjie Hu: Shape-shifting in the endoplasmic reticulum.

Hu J, Powell K.

J Cell Biol. 2015 Jun 8;209(5):626-7.

PMID: 26056135 

 

Human atlastin GTPases mediate differentiated fusion of endoplasmic reticulum membranes.

Hu X, Wu F, Sun S, Yu W, Hu J.

Protein Cell. 2015 Apr;6(4):307-311.

PMID: 25773277

 

Cis and trans interactions between atlastin molecules during membrane fusion.

Liu TY, Bian X, Romano FB, Shemesh T, Rapoport TA, Hu J.

Proc Natl Acad Sci U S A. 2015 Apr 14;112(15):E1851-60.

PMID: 25825753

 

Comparison of human and Drosophila atlastin GTPases.

Wu F, Hu X, Bian X, Liu X, Hu J.

Protein Cell. 2015 Feb;6(2):139-46.

PMID: 25407413 

 

Structural Basis of the Differential Function of the Two C. elegans Atg8 Homologs, LGG-1 and LGG-2, in Autophagy.

Wu F, Watanabe Y, Guo XY, Qi X, Wang P, Zhao HY, Wang Z, Fujioka Y, Zhang H, Ren JQ, Fang TC, Shen YX, Feng W, Hu J, Noda NN, Zhang H.

Mol Cell. 2015 Dec 17;60(6):914-29.

PMID: 26687600

 

Structures of the yeast dynamin-like GTPase Sey1p provide insight into homotypic ER fusion.

Yan L, Sun S, Wang W, Shi J, Hu X, Wang S, Su D, Rao Z, Hu J, Lou Z.

J Cell Biol. 2015 Sep 14;210(6):961-72.

PMID: 26370501


2013

Homotypic fusion of endoplasmic reticulum membranes in plant cells.

Zhang M, Hu J.

Front Plant Sci. 2013 Dec 18;4:514.

PMID: 24385977 Review.

 

Structural insight into Golgi membrane stacking by GRASP65 and GRASP55 proteins.

Feng Y, Yu W, Li X, Lin S, Zhou Y, Hu J, Liu X.

J Biol Chem. 2013 Sep 27;288(39):28418-27.

PMID: 23940043 

 

ROOT HAIR DEFECTIVE3 family of dynamin-like GTPases mediates homotypic endoplasmic reticulum fusion and is essential for Arabidopsis development.

Zhang M, Wu F, Shi J, Zhu Y, Zhu Z, Gong Q, Hu J.

Plant Physiol. 2013 Oct;163(2):713-20.

PMID: 23922269 

 

Differential roles of the C and N termini of Orai1 protein in interacting with stromal interaction molecule 1 (STIM1) for Ca2+ release-activated Ca2+ (CRAC) channel activation.

Zheng H, Zhou MH, Hu C, Kuo E, Peng X, Hu J, Kuo L, Zhang SL.

J Biol Chem. 2013 Apr 19;288(16):11263-72.

PMID: 23447534


2012

Molecular basis for sculpting the endoplasmic reticulum membrane.

Lin S, Sun S, Hu J.

Int J Biochem Cell Biol. 2012 Sep;44(9):1436-43.

PMID: 22640864 Review.

 

Lipid interaction of the C terminus and association of the transmembrane segments facilitate atlastin-mediated homotypic endoplasmic reticulum fusion.

Liu TY, Bian X, Sun S, Hu X, Klemm RW, Prinz WA, Rapoport TA, Hu J.

Proc Natl Acad Sci U S A. 2012 Aug 7;109(32):E2146-54.

PMID: 22802620

 

The dynamin-like GTPase Sey1p mediates homotypic ER fusion in S. cerevisiae.

Anwar K, Klemm RW, Condon A, Severin KN, Zhang M, Ghirlando R, Hu J, Rapoport TA, Prinz WA.

J Cell Biol. 2012 Apr 16;197(2):209-17.

PMID: 22508509


2011

Weaving the web of ER tubules.

Hu J, Prinz WA, Rapoport TA.

Cell. 2011 Dec 9;147(6):1226-31.

PMID: 22153070 Review.

 

Structures of the atlastin GTPase provide insight into homotypic fusion of endoplasmic reticulum membranes.

Bian X, Klemm RW, Liu TY, Zhang M, Sun S, Sui X, Liu X, Rapoport TA, Hu J.

Proc Natl Acad Sci U S A. 2011 Mar 8;108(10):3976-81.

PMID: 21368113 

 

Mutations in Orai1 transmembrane segment 1 cause STIM1-independent activation of Orai1 channels at glycine 98 and channel closure at arginine 91.

Zhang SL, Yeromin AV, Hu J, Amcheslavsky A, Zheng H, Cahalan MD.

Proc Natl Acad Sci U S A. 2011 Oct 25;108(43):17838-43.

PMID: 21987804


2009

Mechanisms shaping the membranes of cellular organelles.

Shibata Y, Hu J, Kozlov MM, Rapoport TA.

Annu Rev Cell Dev Biol. 2009;25:329-54.

PMID: 19575675

 

A class of dynamin-like GTPases involved in the generation of the tubular ER network.

Hu J, Shibata Y, Zhu PP, Voss C, Rismanchi N, Prinz WA, Rapoport TA, Blackstone C.

Cell. 2009 Aug 7;138(3):549-61.

PMID: 19665976 


2008

The reticulon and DP1/Yop1p proteins form immobile oligomers in the tubular endoplasmic reticulum.

Shibata Y, Voss C, Rist JM, Hu J, Rapoport TA, Prinz WA, Voeltz GK.

J Biol Chem. 2008 Jul 4;283(27):18892-904.

PMID: 18442980

 

Membrane proteins of the endoplasmic reticulum induce high-curvature tubules.

Hu J, Shibata Y, Voss C, Shemesh T, Li Z, Coughlin M, Kozlov MM, Rapoport TA, Prinz WA.

Science. 2008 Feb 29;319(5867):1247-50.

PMID: 18309084


2006

Structural basis for phosphotyrosine recognition by the Src homology-2 domains of the adapter proteins SH2-B and APS.

Hu J, Hubbard SR.

J Mol Biol. 2006 Aug 4;361(1):69-79.

PMID: 16824542

 

Activation-dependent substrate recruitment by the eukaryotic translation initiation factor 2 kinase PERK.

Marciniak SJ, Garcia-Bonilla L, Hu J, Harding HP, Ron D.

J Cell Biol. 2006 Jan 16;172(2):201-9.

PMID: 16418533


2005

Structural characterization of a novel Cbl phosphotyrosine recognition motif in the APS family of adapter proteins.

Hu J, Hubbard SR.

J Biol Chem. 2005 May 13;280(19):18943-9.

PMID: 15737992

 

Structural basis for inhibition of the insulin receptor by the adaptor protein Grb14.

Depetris RS, Hu J, Gimpelevich I, Holt LJ, Daly RJ, Hubbard SR.

Mol Cell. 2005 Oct 28;20(2):325-33.

PMID: 16246733


2003

Structural basis for recruitment of the adaptor protein APS to the activated insulin receptor.

Hu J, Liu J, Ghirlando R, Saltiel AR, Hubbard SR.

Mol Cell. 2003 Dec;12(6):1379-89.

PMID: 14690593



科研活动



科研项目:

1.  胞生物自噬过程中膜的构建于融合,参与,国家级,2015-01--2018-12 
2.  中组部青年拔尖人才,主持,国家级,2014-01--2015-12
3.  RHD3影响内质网形态和根毛生长的分子机制,主持,国家级,2012-01--2015-12
4.  美国霍华德休斯国际青年科学家奖基金,主持,其他级,2012-01--2016-12
5.  嵌膜GTP酶影响内质网结构的分子机制,主持,国家级,2010-01--2012-12
6.  生物膜形态发生及维持的分子机制,主持,国家级,2010-01--2014-12

参与会议:

1. “Membrane Shaping and Remodeling by Proteins”   May 21-23, 2010 (第一届蛋白质介导的膜塑形与重装”国际学术研讨会) 会议组织者
2. “Membrane Shaping and Remodeling by Proteins”  May 16-19,2013 (第二届蛋白质介导的膜塑形与重装”国际学术研讨会)会议组织者 
3. EMBO work shop—cell cellfusion.2013, invited speaker. 
报告题目:Mechanistic insight into mitofusin-mediated membrane fusion 
4. IUPAB2014国际生物物理大会
报告题目:Homotypic membrane fusion by dynamin-like GTPases


科研项目
( 1 ) 嵌膜GTP酶影响内质网结构的分子机制, 负责人, 国家任务, 2010-01--2012-12
( 2 ) 生物膜形态发生及维持的分子机制, 负责人, 国家任务, 2010-01--2014-12
( 3 ) RHD3影响内质网形态和根毛生长的分子机制, 负责人, 国家任务, 2012-01--2015-12
( 4 ) 美国霍华德休斯国际青年科学家奖基金, 负责人, 其他国际合作项目, 2012-01--2016-12
( 5 ) 中组部青年拔尖人才, 负责人, 国家任务, 2014-01--2015-12
( 6 ) 细胞生物自噬过程中膜的构建与融合, 负责人, 国家任务, 2015-01--2020-12
( 7 ) 细胞器动态互作的蛋白质机器, 负责人, 国家任务, 2016-07--2021-06
( 8 ) 内质网管状网络的生理功能研究, 负责人, 国家任务, 2017-01--2021-12
( 9 ) 内质网相关细胞器互作在细胞应激反应中的机制与功能研究, 负责人, 国家任务, 2019-01--2022-12
( 10 ) 衰老过程中细胞代谢和细胞器稳态失衡, 负责人, 中国科学院计划, 2020-01--2025-12
( 11 ) 新型冠状病毒重塑宿主细胞关键细胞器的机制研究, 负责人, 国家任务, 2021-12--2026-11
( 12 ) 基础研究领域优秀青年团队项目-全人工合成细胞, 负责人, 中国科学院计划, 2022-01--2027-12
( 13 ) 片状内质网的调控与生理功能研究, 负责人, 国家任务, 2023-01--2027-12

招生信息


招生专业:细胞生物学

招生方向:内质网形态与功能
招生专业
071009-细胞生物学
招生方向
细胞器塑形与功能

所获荣誉

1. Structures of the atlastin GTPase provide insight into homotypic fusion of endoplasmic reticulum membranes.入选中国百篇最具影响国际学术论文 2011
2. 美国霍华德休斯医学院(HHMI)国际青年科学家奖 2012
3. 中国科学报社 第三届“青年科学之星”称号 2012
4. 天津青年五四奖章 2012
5. 国家自然科学基金委杰出青年基金 2013
6. 中组部青年拔尖人才 2014
7. 入选**** B类 2015