Biochemistry and Molecular Biology (BIO)
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
Cytoplasmic dynein is a motor protein that transports a variety of cargoes including vesicles/organelles, proteins and mRNAs along microtubules. Its proper function is crucial for human health as mutations in dynein or its regulators, such as dynactin and Lis1, are causally linked to brain developmental disorders and neurodegenerative diseases. We are interested in how dynein finds and attaches to its cargoes including early endosomes and our current objective is to use the filamentous fungus Aspergillus nidulans as a model system to study how dynein is recruited to early endosomes.
A. nidulans is an excellent system for studying dynein function and regulation. In A. nidulans, dynein accumulates at the microtubule plus end near the hyphal tip in a kinesin-1- and dynactin-dependent manner, which places the dynein motor in close proximity with the early endosome cargo. A few years ago we found that the dynein-early endosome interaction in A. nidulans specifically requires the p25 subunit of dynactin. Based on the phenotype of the p25 null mutant, we performed a genetic screen to uncover the unknown molecular machinery linking dynein-dynactin to early endosomes.
Our genetic approach has allowed us to identify two key proteins, HookA (Hook in A. nidulans) and FhipA (FHIP in A. nidulans), which link dynein-dynactin to early endosomes. FhipA is required for the C-terminus of HookA to bind early endosome. The N-terminal part of HookA is important for the HookA-dynein-dynactin interaction, which intriguingly requires not only dynactin p25 but also the dynein complex. We will investigate the mechanisms of the HookA-dynein-dynactin and the FhipA-early endosome interactions. We will also continue to discover and study additional novel proteins regulating dynein-mediated early endosome transport.
Current lab members
Xuanli (Lia) Yao
Selected Recent Publications
Research Articles (* co-first or co-corresponding authors):
- Pantazopoulou, A., Pinar, M., Xiang, X., Peñalva, M.A. (2014) Maturation of late Golgi cisternae into RabERAB11 exocytic post-Golgi carriers visualized in vivo. Mol. Biol. Cell. 25, 2428-2443.
- Yao, X., Wang, X., Xiang, X. (2014) FHIP and FTS proteins are critical for dynein-mediated transport of early endosomes in Aspergillus. Mol. Biol. Cell. 25, 2181-2189. (highlighted by MBoC Highlights)
- Zhang, J*., Qiu, R*., Arst, H.N. Jr, Peñalva, M.A., Xiang, X. (2014) HookA is a novel dynein-early endosome linker critical for cargo movement in vivo. J. Cell Biol. 204, 1009-1026. (highlighted by JCB In Focus and by Nature Reviews Molecular Cell Biology Research Highlight)
- 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. 70, 215-227.
- 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.
- 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-early endosome interaction but not for dynein ATPase activation. J. Cell Sci. 123, 3596-3604.
- 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.