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Synaptic Function Section - Division of Intramural Research

Zu-Hang Sheng Image

Zu-Hang Sheng, Ph.D., Senior Investigator

Dr. Sheng received his Ph.D. degree from the University of Pennsylvania where he worked with Roland Kallen and Robert Barchi in cloning skeletal muscle sodium channel genes and studying their regulatory expression. He did his postdoctoral research in the laboratory of William Catterall at the University of Washington studying structural and functional coupling of presynaptic calcium channels and the synaptic vesicle docking/fusion machinery. Dr. Sheng joined NINDS as an investigator in 1996 and is now a senior investigator and Chief of Synaptic Functions Section. Dr. Sheng's laboratory focuses on the mechanisms regulating axonal transport of mitochondria, endocytic organelles, and synaptic cargoes and their impact on axonal homeostasis, synaptic functions and neurodegeneration.

Laboratory Staff

Xiu-Tang Cheng, M.D., Graduate Student
Jerome Di Giovanni, Ph.D., Postdoctoral Fellow
Adam L Knight, M.S., Graduate Student
Mei-Yao Lin, Ph.D., Postdoctoral Fellow
Natalia Morsci, Ph.D., Postdoctoral Fellow
Rajat Puri, Ph.D., Postdoctoral Fellow
Tao Sun, Ph.D., Research Fellow
Yu-Xiang Xie, Ph.D., Research Fellow
Bin Zhou, Ph.D., Postdoctoral Fellow
Zu-Hang Sheng Staff Image

Research Interests

Proper neuronal function requires integration of the transport of synaptic components and the assembly and regulation of synaptic structures and function. Neurons also require specialized mechanisms to transport mitochondria to axons and retain them in the vicinity of synaptic terminals where energy production and calcium homeostasis are in high demand. Synaptic structure and function undergo activity-dependent remodeling, thereby altering axonal transport. In addition, neurons maintain cellular homeostasis through the retrograde transport of signaling complexes and late endocytic organelles to the cell body. Maintaining efficient degradation capacities in the autophagy-lysosomal system is essential for quality control of intracellular components.

Our research goal is to elucidate the mechanisms regulating organelle transport and membrane trafficking and their impact on synaptic function and axonal degeneration. We are addressing the following questions: (1) What is the mechanism regulating axonal transport and distribution of mitochondria and late endocytic organelles? (2) How does their transport impact synaptic formation and plasticity, cellular homeostasis, and axonal degeneration? (3) What is the mechanism synchronizing synaptic transmission? To address these issues, we have combined molecular and cellular approaches, and live-cell imaging with a multidisciplinary systems analysis of genetically engineered mice. This analysis provides us with a foundation to better understand the physiological roles of syntaphilin, syntabulin, and Snapin in the neuronal transport and synaptic transmission.

Dysfunction and altered transport of mitochondria, and defective autophagy-lysosomal function have been implicated in the pathogenesis of some neurodegenerative diseases. Our long-term goal is to identify the cellular pathways (1) for turnover of dysfunctional mitochondria through mitophagy, and (2) for clearance of aggregation-prone proteins by regulating the autophagy-lysosomal system. Pursuing these investigations will advance our knowledge of fundamental processes that may affect human neurological disorders and is thus the very essence of NINDS mission.

Selected Recent Publications

  • Tao Sun, Haifa Qiao, Ping-Yue Pan, Yanming Chen, and Zu-Hang Sheng
    Mobile axonal mitochondria contribute to the variability of presynaptic strength, Cell Reports, 2013, pp. (see Video Summary: Full Text/Abstract
  • Yanmin Chen and Zu-Hang Sheng
    Kinesin-1–syntaphilin coupling mediates activity-dependent regulation of axonal mitochondrial transport , Journal of Cell Biology, 2013, vol. 202, pp. 351-364 (Also see "In Focus" article by Ben Short). Full Text/Abstract
  • Qian Cai, Hesham Mostafa Zakaria, Anthony Simone, and Zu-Hang Sheng
    Spatial Parkin Translocation and Degradation of Depolarized Mitochondria via Mitophagy in Live Cortical Neurons, Current Biology, 2012, vol. 22, pp. 545-552. Full Text/Abstract
  • Zu-Hang Sheng & Qian Cai
    Mitochondrial Transport in Neurons: Impact on Synaptic Homeostasis and Neurodegeneration (Review article), Nature Reviews Neuroscience, 2012, vol. 13, pp. 77-93. Full Text/Abstract
  • Bing Zhou, Qian Cai, Yuxiang Xie, and Zu-Hang Sheng
    Snapin recruits dynein to BDNF-TrkB signaling endosomes for retrograde axonal transport and is essential for dendrite growth of cortical neurons, Cell Reports, 2012, vol. 2, pp. 42-51. Full Text/Abstract
  • Qian Cai, Li Lu, Jin-Hua Tian, Yi-Bing Zhu, Haifa Qiao, and Zu-Hang Sheng
    Snapin-regulated late endosomal transport is critical for efficient autophagy-lysosomal function in neurons, Neuron, 2010, vol. 68, pp. 73-86, (Also see Preview by M. Yuzaki). Full Text/Abstract
  • Jian-Sheng Kang, Jin-Hua Tian*, Ping-Yue Pan*, Philip Zald, Cuiling Li, Chuxia Deng, and Zu-Hang Sheng
    Docking of Axonal Mitochondria by Syntaphilin Controls their Mobility and Affects Short-term Facilitation (*equal contribution), Cell, 2008, vol. 132, pp. 137-248. Full Text/Abstract
  • Guifang Lao, Volker Scheuss, Claudia M. Gerwin, Qingning Su, Sumiko Mochida, Jens Rettig, and Zu-Hang Sheng.
    Syntaphilin: a syntaxin-1 clamp that controls SNARE assembly, Neuron, 2000, vol. 25, pp. 191-201.

Selected Earlier Publications

Contact Information

Synaptic Function Section, NINDS
Porter Neuroscience Research Center
Building 35, Room 2B-215
35 Convent Drive, MSC 3706
Bethesda, MD 20892-3706

Telephone: 301-435-4596 (office), 301-451-9669 (laboratory), 301-480-5763 (fax)