Uniformed Services University of the Health Sciences
Department of Biochemistry and Molecular Biology
4301 Jones Bridge Road, C1094
Bethesda, Maryland 20814-4799
Office: (301) 295-0000
Fax: (301) 295-3512
Lab: (301) 295-3571
- B.S. & M.S. Department of Biology, Peking University, Beijing, P. R. China
- Ph.D. Department of Biochemistry, UMDNJ-Robert Wood Johnson Medical School, Piscataway, New Jersey
- Post-doctoral research: Department of Pharmacology, UMDNJ-Robert Wood Johnson Medical School, Piscataway, New Jersey
Intracellular transport of various cellular materials is an essential activity of eukaryotic cells and long-distance cargo transport is especially important in elongated cells such as neurons. In neurons, the minus-end-directed microtubule motor cytoplasmic dynein powers retrograde movement of early endosomes that carry signaling molecules to the nucleus, which is crucial for neuronal survival. Mutations in the dynein-interacting complex, dynactin, cause the devastating neurodegenerative disease amyotrophic lateral sclerosis (ALS). As a subproject of the Neuroplasticity group within the Center of Neuroscience and Regenerative Medicine (CNRM) at USUHS, we will investigate the role of dynein in neuronal regeneration upon injury of the central nervous system by using a mouse injury model.
To study the mechanism of dynein-early-endosome interaction, we will use Aspergillus nidulans, a filamentous fungus, as a genetic model system. The power of A. nidulans genetics has had a great impact on the understanding of neuronal dynein regulation by linking NUDF, a homolog of the human brain disease protein LIS1 (lissencephaly 1) to the dynein pathway through a genetic analysis of the fungal nuclear distribution (nud) mutants. We have developed methods for visualizing dynein and dynactin in vivo and for purifying the dynein and dynactin complexes in A. nidulans, and we have been using a combination of genetic, live-cell imaging and biochemical approaches to determine the specific roles of proteins and/or specific domains of proteins in the dynein pathway. In elongated hyphae of filamentous fungi, dynein, dynactin and NUDF/LIS1 all accumulate at the dynamic microtubule plus ends near the hyphal tip, where dynein may interact with early endosomes for their minus-end-directed transport. Our previous studies have revealed that kinesin-1 and the dynactin complex are important for the plus-end accumulation of dynein, and our recent studies suggest that the dynactin complex is also important for linking plus-end dynein to early endosomes. We are currently focusing on the p25 protein of the dynactin complex to determine its role in dynein-early-endosome interaction. Based on the phenotype of the p25 deletion mutant, we have developed a classic genetic strategy well suited for identifying other novel bridging factors and/or regulators involved in linking dynein to early endosomes in vivo.
Current lab members
Research Assistant Professor
B.S. Shanghai Medical University
Ph.D. Beijing Medical University
Rongde Qiu Research Associate
B.S. Fudan University
M.S. Institute of Biochemistry
& Cell Biology, SIBS, CAS
Xuanli (Lia) Yao
B.S. Nanjing University
Ph.D. Ohio State University
Selected Recent Publications
Research Articles (* co-first or co-corresponding authors):
- Zhang, J., Twelvetrees, A.E., Lazarus, J.E., Blasier, K.R., Yao, X., Inamdar, N.A., Holzbaur, E.L.F.*, Pfister, K.K.*, Xiang, X.* (2013) Establishing a novel knock-in mouse line for studying neuronal cytoplasmic dynein under normal and pathologic conditions. Cytoskeleton. In press
- Qiu, R., Zhang, J., Xiang, X. (2013) Identification of a novel site in the tail of dynein heavy chain important for dynein function in vivo. J. Biol. Chem. 288, 2271-2280.
- Yao, X., Zhang, J., Zhou, H., Wang, E., Xiang, X. (2012) In vivo roles of the basic domain of dynactin p150 in microtubule plus-end tracking and dynein function. Traffic 13, 375-387.
- Zhang, J.*, Yao, X.*, Fischer, L. Abenza J. F., Peñalva. M. A., Xiang, X. (2011) The p25 subunit of the dynactin complex is required for dynein-early endosome interaction. J. Cell Biol. 193, 1245-1255.
- Zhang, J., Tan, K., Wu, X., Chen, G., Sun, J., Reck-Peterson, S., Hammer, J.A. III*, Xiang, X.* (2011) Aspergillus myosin-V supports polarized growth in the absence of microtubule-based transport. PLoS ONE, 6(12):e28575. Epub 2011 Dec 14.
- Zhang, J., Zhuang, L., Lee, Y. Abenza J. F., Peñalva. M. A., Xiang, X. (2010) The microtubule-plus-end localization of Aspergillus dynein is important for dynein-earlyendosome interaction but not for dynein ATPase activation. J. Cell Sci. 123, 3596-3604.
- Zhai, B.*, Zhou, H.*, Yang, L., Zhang, J., Jung, K., Giam, C.Z., Xiang, X., Lin X. (2010) Polymyxin B, in combination with fluconazole, exerts a potent fungicidal effect. J. Antimicrob. Chemother. 65, 931-938.
- Zhang, J.*, Li, S.*, Musa, S., Zhou, H., Xiang, X. (2009) Dynein light intermediate chain in Aspergillus nidulans is essential for the interaction between heavy and intermediate chains. J. Biol. Chem. 284, 34760-34768.
- Zhang, J., Wang, L., Zhuang, L., Huo, L., Musa, S., Li, S., Xiang, X. (2008) Arp11 affects dynein-dynactin interaction and is essential for dynein function in Aspergillus nidulans. Traffic 9, 1073-1087.
- Zhuang, L.*, Zhang, J.*, Xiang, X. (2007) Point mutations in the stem region and the fourth AAA domain of cytoplasmic dynein heavy chain partially suppress the phenotype of NUDF/LIS1 loss in Aspergillus nidulans. Genetics 175, 1185-1196.
- Efimov, V.P.*, Zhang, J.*, Xiang, X. (2006) CLIP-170 homologue and NUDE play overlapping roles in NUDF localization in Aspergillus nidulans. Mol Biol Cell 17, 2021-2034.
- Xiang, X. (2012) Nuclear Positioning: dynein needed for microtubule shrinkage-coupled movement (dispatch). Curr. Biol. 22, R496-499.
- Xiang, X. (2011) Insights into Cytoplasmic Dynein Function and Regulation from Fungal Genetics (book chapter). In Dyneins: Structure, Biology and Disease (Edited by S. M. King), Elsevier. p455-481.
- Xiang, X. and Oakley, B. R. (2010). The Cytoskeleton in Filamentous Fungi (book chapter). In: Cellular and Molecular Biology of Filamentous Fungi (Edited by K. Borkovich and D. Ebbole), ASM Press. p209-223.
- Oakley, B. R. and Xiang, X. (2007) Fluorescent Labels for Intracellular Structures and Organelles (book chapter). In: The Aspergilli: Genomics, Medical Aspects, Biotechnology, and Research Methods (Edited by G. Goldman and S. A. Osmani), Taylor and Francis, CRC Press. p513-525.
- Wu, X., Xiang, X., Hammer, J. (2006) Motor proteins at microtubule plus end. (review), Trends in Cell Biology 16,135-143.
- Xiang, X. (2006) A +TIP for a smooth trip. (minireview) J. Cell Biol. 172, 651-654.