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    Name:
    LI Xiangdong
    Subject:
    Biochemistry and Molecular Biology
    Tel/Fax:
    +86-10-64806015 (Office); +86-10-64806280 (Lab)  /  +86-10-64806015
    E-mail:
    lixd@ioz.ac.cn
    Address:
    The State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, 1 Beichen West Road, Chaoyang District, Beijing 100101, P.R.China
    More:
    Group of Cell Motility and Muscle Contraction      

    Resume:
    1990-1993, Institute of Entomology, Chinese Academy of Sciences, M.S. student
    1993-1996, Institute of Biochemistry, Chinese Academy of Sciences, Ph.D student
    1996-2004, Department of Physiology, University of Massachusetts Medical School, postdoctoral fellow
    2004-2008, Department of Physiology, University of Massachusetts Medical School, instructor and research assistant professor
    2008-2009, Department of Cell Biology, University of Massachusetts Medical School, research assistant professor
    2009-, Institute of Zoology, Chinese Academy of Sciences, professor
    Research Interest:

    My primary research interests centers on the roles played by motor proteins and cytoskeletal proteins in driving cell motility and muscle contraction. Currently, my Lab researches on the structure, function, and regulation of unconventional myosins and muscle myosins utilizing a variety of techniques including cell culture, live cell imaging, TIRF, molecular biology, and biochemistry.

    1. Structure and function of unconventional myosin

    Besides being a key component of muscle, myosins exist in all types of eukaryotic cells. With the completion of a number of eukaryotic genomic projects, it became apparent that the myosin superfamily is much larger and more diverse than previously predicted. Currently, the myosin superfamily is organized in more than 35 classes, based on structural similarities. Although the functions of conventional myosins in muscle contraction and cell division have been intensively studied, little is known about the unconventional myosin. We are currently investigating two unique unconventional myosins, myosin-19 and myosin-20.
    Myosin-19 is a vertebrate-specific myosin and is exclusively localized in mitochondria. Recently, we found that myosin-19 is a high-duty ratio molecular motor moving to the plus-end of the actin filament (JBC 2014). We are currently investigating the role of myosin-19 on mitochondria biology. Myosin-20 is an insect-specific myosin. Drosophila myosin-20 functions as a crucial downstream component of the Fat signaling pathway, influencing growth, affinity, and gene expression during development. We have recently shown that Drosophila myosin-20 functions as a scaffold protein, but not as a molecular motor, in a signaling pathway controlling cell differentiation (Biochem 2014).

    2. Molecular regulation of unconventional myosin-5.

    Myosin-5 (Myo5) is so far the best characterized unconventional myosin in term of cellular function and molecular regulation. Myo5 is widely expressed in almost all eukaryotes and implicated in a number of vesicles trafficking and tethering. We are particularly interested in how the motor function of Myo5 is regulated. We proposed a tail-inhibition model for the regulation of vertebrate Myo5a: The globular tail domain (GTD) of Myo5a is the inhibitory domain, which interacts with the head and inhibit its motor function; cargo-binding, high Ca2+ levels and/or phosphorylation may reduce the head-GTD interaction, thus activating the motor activity (BBRC 2004, JBC 2006, PNAS 2008). This model for the regulation of Myo5 is well accepted in the field and becomes a paradigm for the regulation of unconventional myosin.
    We found that vertebrate Myo5b and Myo5c, as well as Drosophila Myo5 is regulated by the GTD in a Ca2+-dependent manner (Cell 2008, JBC 2016a, Biochem J 2015), suggesting that tail-inhibition mechanism is conserved for class V myosins. We demonstrated that the GTD functions as a dimer in inhibiting the motor function of the head (JBC 2016b) and proposed that cargo-binding allosterically abolishes the head-GTD interaction, thus activating the motor function (Sci Rep 2015). We identified the calmodulin bound to the first IQ motif of Myo5a as the key for Ca2+ activation (JBC 2012). We solved the structure of myosin-5a in complex with Ca2+-bound calmodulin and characterized Ca2+ transition in the complex, and proposed that the calmodulin in complex with IQ motif functions as an intact Ca2+ sensor (PNAS 2016).

    3. Molecular mechanism of insect muscle development

    The migratory Locusts (Locusta migratoria) are important agricultural pests in China. The plague of Locusts is associated with the strong ability in moving and flying, which depends on locust muscle system. Striated muscle myosin is the most important functional protein in muscle. We found that, contrary to vertebrates, locust has only one striated muscle myosin gene, containing six alternative splicing exons in Locust myosin gene. In theory, locust myosin gene encodes 360 types of myosin (IMB 2016). We are currently investigating how the alternative splicing exons affect the function of Locust muscle myosin and how the alternative splicing exons of Locust myosin is regulated.


    Public Services:

    Awards and Honors:

    Research Grants:
    The National Natural Science Foundation of China, the National Basic Research Program of China.
    Selected Publication:
    1. Mei Shen#, Ning Zhang#, Sanduo Zheng#, Wen-Bo Zhang, Hai-Man Zhang, Zekuan Lu, Qian Peter Su, Yujie Sun, Keqiong Ye, and Xiang-dong Li* (2016) Calmodulin in complex with the first IQ motif of myosin-5a functions as an intact calcium sensor. Proceedings of the National Academy of Sciences USA 113: E5812-E5820.
    2. Jing Li, Zekuan Lu, Jing He, Qianquan Chen, Xianhui Wang, Le Kang, and Xiang-dong Li* (2016) Alternative Exon-encoding Regions of Locusta migratoria Muscle Myosin Modulate the pH dependence of ATPase Activity. Insect Molecular Biology 25:689–700.
    3. Nan Chen, Yong-Liang Fan*, Yu Bai, Xiang-dong Li, Zhan-Feng Zhang, and Tong-Xian Liu* (2016) Cytochrome P450 gene, CYP4G15, modulates hydrocarbon production in the pea aphid, Acyrthosiphon pisum. Insect Biochemistry and Molecular Biology 76: 84-94.
    4. Wen-Bo Zhang, Lin-Lin Yao, and Xiang-dong Li* (2016) The Globular Tail Domain of Myosin-5a Functions As a Dimer in Regulating the Motor Activity Journal of Biological Chemistry 291: 13571 -13579.
    5. Lin-Lin Yao, Mei Shen, Zekuan Lu, Mitsuo Ikebe, and Xiang-dong Li* (2016) Identification of the isoform-specific interactions between the tail and the head of class V myosin. Journal of Biological Chemistry 291: 8241-8250.
    6. Hanna Witwick, Hong Jia, Artem Kutikov, Pablo Reyes-Gutierrez, Xiang-dong Li, Paul R. Odgren* (2015) TRAFD1 (FLN29) Interacts with Plekhm1 and Regulates Osteoclast Acidification and Resorption. PLOS ONE 10: e0127537
    7. Chengqi Zhang#, Yun Chen#, Yanni Yin, Huan-Hong Ji, Won-Bo Shim, Yiping Hou, Mingguo Zhou*, Xiang-dong Li*, and Zhonghua Ma* (2015) A small molecule species-specifically inhibits Fusarium myosin I. Environmental Microbiology 17(8): 2735–2746.
    8. Huan-Hong Ji, Hai-Man Zhang, Mei Shen, Lin-Lin Yao, Xiang-dong Li* (2015) The motor function of Drosophila melanogaster myosin-5 is activated by calcium and cargo-binding protein dRab11. Biochemical Journal 469 (1):135-144.
    9. Lin-Lin Yao#, Qing-Juan Cao#, Hai-Man Zhang#, Jie Zhang, Yang Cao, and Xiang-dong Li* (2015) Melanophilin Stimulates Myosin-5a Motor Function by Allosterically Inhibiting the Interaction between the Head and Tail of Myosin-5a. Scientific Reports 5:10874.
    10. Zekuan Lu, Xiao-Nan Ma, Hai-Man Zhang, Huan-Hong Ji, Hao Ding, Jie Zhang, Dan Luo, Yujie Sun, and Xiang-dong Li* (2014) Mouse Myosin-19 is a Plus-end-directed, High-duty Ratio Molecular Motor. Journal of Biological Chemistry 289: 18535–18548.
    11. Yang Cao, Howard D. White, and Xiang-dong Li* (2014) Drosophila myosin-xx functions as an actin-binding protein to facilitate the interaction between zyx102 and actin. Biochemistry 53, 350–360.
    12. Rong-Na Ma, Katsuhide Mabuchi, Jing Li, Zekuan Lu, Chih-Lueh Albert Wang, and Xiang-dong Li* (2013) Cooperation between the Two Heads of Smooth Muscle Myosin Is Essential for Full Activation of the Motor Function by Phosphorylation. Biochemistry 52, 6240?6248.
    13. Zekuan Lu#, Mei Shen#, Yang Cao, Hai-Man Zhang, Lin-Lin Yao, Xiang-dong Li* (2012) Calmodulin bound to the first IQ motif is responsible for calcium-dependent regulation of myosin 5a. Journal of Biological Chemistry 287: 16530-16540 (#, equal contribution).
    14. 曹洋,沈梅,张洁,李向东* (2011) 果蝇非常规肌球蛋白的结构与功能.应用昆虫学报 48: 239-246.
    15. Nobuhisa Umeki, Hyun Suk Jung, Shinya Watanabe, Tsuyoshi Sakai, Xiang-dong Li, Reiko Ikebe, Roger Craig, and Mitsuo Ikebe* (2009The tail binds to the head-neck domain, inhibiting ATPase activity of myosin VIIA Proceedings of the National Academy of Sciences USA 106:8483-8.
    16. Xiang-dong Li*, Hyun Suk Jung, Qizhi Wang, Reiko Ikebe, Roger Craig, and Mitsuo Ikebe (2008) The globular tail domain puts on the brake to stop the ATPase cycle of the myosin Va. Proceedings of the National Academy of Sciences USA 105: 1140-1145 (Citied in “Faculty of 1000”).
    17. Zhiping Wang, Jeffrey G. Edwards, Nathan Riley, D. William Provance, Jr., Ryan Karcher, Xiang-dong Li, Ian G. Davison, Mitsuo Ikebe, John A. Mercer, Julie A. Kauer, and Michael D. Ehlers* (2008) Myosin Vb mobilizes recycling endosomes and AMPA receptors for postsynaptic plasticity. Cell 135, 535-548.
    18. Osamu Sato, Xiang-dong Li, and Mitsuo Ikebe* (2007) Myosin Va becomes a low duty ratio motor in the inhibited form. Journal of Biological Chemistry 282:13228-13239.
    19. Xiang-dong Li*, Hyun Suk Jung, Katsuhide Mabuchi, Roger Craig, and Mitsuo Ikebe (2006) The globular tail domain of myosin Va functions as an inhibitor of the myosin Va motor. Journal of Biological Chemistry 281:21789-21798 (Citied in “Faculty of 1000”).
    20. Xiang-dong Li, Reiko Ikebe, and Mitsuo Ikebe* (2005) Activation of Myosin Va function by melanophilin, a specific docking partner of Myosin Va. Journal of Biological Chemistry 278: 29435-29441.
    21. Xiang-dong Li, Katsuhide Mabuchi, Reiko Ikebe, and Mitsuo Ikebe* (2004) Ca2+ induced activation of ATPase activity of myosin Va is accompanied with a large conformational change. Biochemical and Biophysical Research Communications 315: 538-545.
    22. Xiang-dong Li and Mitsuo Ikebe* (2003) Two functional heads are required for full activation of smooth muscle myosin. Journal of Biological Chemistry 278: 29435-29441.
    23. Yu Chen, Norio Takizawa, Jessica L Crowley, Sang W. Oh, Cheryl L. Gatto, Taketoshi Kambara, Osamu Sato, Xiang-dong Li, Mitsuo Ikebe, and Elizabeth J. Luna* (2003) F-actin and myosin II binding domains in supervillin. Journal of Biological Chemistry  278:46094-46106
    24. Xin Zhou, Xiang-dong Li, Jian-zhong Yuan, Zhen-hua Tang, and Wang-yi Li* (2000) Toxicity of Cinnamomin-A new type II ribosome-inactivating protein to ballworm and mosquito. Insect Biochemistry and Molecular Biology 30(3): 259-264
    25. Xiang-dong Li, Junya Saito, Reiko Ikebe, Katsuhide Mabuchi, and Mitsuo Ikebe* (2000) The interaction between the regulatory light chain domains on two heads is critical for regulation of smooth muscle myosin. Biochemistry 39(9): 2254-2260.
    26. Xiang-dong Li, Troy E. Rhodes, Reiko Ikebe, Taketoshi Kambara, Howard D. White and Mitsuo Ikebe* (1998) Effects of mutations in the g-phosphate binding site of myosin on its motor function. Journal of Biological Chemistry 273(42): 27404-27411.
    27. Wang-yi Liu*, Huai-yang Chen, Wen-feng Chen, Xiang-dong Li, Norbert Ulbrich and Werner Schroder (1997) A proposed position of a disulfide bridge in the molecules of cinnamomin and porrectin-two new type II ribosome-inactivating proteins isolated from the seeds of camphor trees. Biochemistry and Molecular Biology International 44(5): 1045-1049.
    28. Xiang-dong Li, Wen-feng Chen, Wang-yi Liu*, and Gui-hai Wang (1997) Large-scale purification of two new ribosome-inactivating proteins --- cinnamomin and camphorin from the seed of Cinnamomum camphora. Protein Expression and Purification 10:27-31.
    29. 李向东,刘望夷* (1997) 核糖体失活蛋白研究进展。生命的化学17(2): 15-18.
    30. 李向东,刘望夷* (1997) 核糖体失活蛋白结构功能与分布。细胞生物学杂志19(2): 69-75.
    31. Xiang-dong Li, Wang-yi Liu*, and Ching-i Niu. (1996)  Purification of a new ribosome-inactivating protein from the seeds of Cinnamomum porrectum and characterization of the RNA N-glycosidase activity of the toxic protein. Biological Chemistry, 377: 825-831.
    32. Jun Ling, Xiang-dong Li, Xiao-hua Wu, and Wang-yi Liu* (1995) Topological requirements for recognition and cleavage of DNA by ribosome-inactivating proteins. Biological Chemistry Hoppe-Seyler, 376: 637-641.
    33. 李向东, 唐振华* (1993) 马拉硫磷羧酸酯酶在小菜蛾抗药性中的作用. 昆虫学研究集刊11: 1-10.