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Ling-Gang Wu, M.D., Ph.D., Senior Investigator

Dr. Wu received his M.D. in 1985 from Second Military Medical College, Shanghai, and his Ph.D. in neuroscience in 1994 from Baylor College of Medicine in Houston, where he worked with Peter Saggau studying how calcium channels control transmitter release. From 1994 to 1996, he was a postdoc in professor William Betz's lab at Univ. Colorado Medical School, where he studied how vesicle endocytosis is regulated. From 1996 to 1999, he was a postdoc in Bert Sakmann's lab at the Max Planck Institute in Heidelberg, Germany, where he studied release mechanisms and short-term synaptic plasticity. From 1999 to 2003 he was an assistant professor at Washington University in St. Louis. Dr. Wu joined NINDS as an investigator in 2003 and was promoted to senior investigator in 2007. His laboratory investigates the fundamental process of synaptic transmission, including how calcium channels control exocytosis, how fusion pores open, close or dilate, how endocytosis is initiated and mediated, and how synaptic plasticity is influenced by calcium channels, fusion pore opening and endocytosis.
Photo of Ling-Gang Wu, M.D., Ph.D., Senior Investigator

Staff:
Staff Photo for Synaptic Transmission Section


Research Interests:
Resolving fusion pore kinetics

The function of our brain relies on synaptic transmission across billions of synapses in the brain. Regulation of synaptic transmission plays essential roles in many physiological and pathological processes, such as control of neuronal network outputs, neuronal development, learning and memory, and neurological diseases. The Synaptic Transmission Section aims at understanding how synaptic transmission, particularly vesicle exo- and endocytosis at nerve terminals, is mediated and regulated.

Synaptic transmission at nerve terminals is mainly composed of 1) calcium influx via voltage-gated calcium channels during depolarization, 2) calcium-triggered vesicle fusion and fusion pore opening, which releases transmitter and thus generates a postsynaptic current, 3) fusion pore dilation or closure, and 4) retrieval of fused vesicle membrane that recycles exocytosed vesicles. We study the molecular mechanisms underlying each of these key steps using an array of advanced techniques, including whole-cell current and capacitance recordings, cell-attached single channel current and capacitance recordings, epi-fluorescence imaging, confocal and TIRF imaging, super-resolution STED imaging, STORM imaging, ion conductance microscopy, and molecular biological techniques such as over expression, knockdown and knockout. We used three preparations, the giant calyx of Held nerve terminal, the cultured hippocampal synapse and the chromaffin cell.

The lab is often seeking talented and motivated postdoctoral candidates with experience in cell biology (e.g., live-cell fluorescence imaging), molecular biology (e.g., mouse genetics), electrophysiology, or imaging (single vesicle or single molecule imaging). The lab is also often seeking graduate students majored in Neurobiology, Cell Biology, Pharmacology, Genetics, and Biomedical Engineering, with an interest in exo- and endocytosis. Contact Dr. Wu for further information.


Selected Recent Publications:
  • Sheng J, He L, Zheng H, Xue L, Luo F, Shin W, Sun T, Kuner T, Yue DT, Wu LG. (2012) Calcium-channel number critically influences synaptic strength and plasticity at the active zone., Nat Neurosci. 15(7), 998-1006. Full Text/Abstract

  • Xue L, McNeil BD, Wu XS, Luo F, He L, Wu LG. (2012) A membrane pool retrieved via endocytosis overshoot at nerve terminals: a study of its retrieval mechanism and role., J Neurosci. 32(10), 3398-404. Full Text/Abstract

  • Xue L, Zhang Z, McNell B, Luo FJ, Wu XS, Sheng J, Shin W, Wu LG (2012) Voltage-Dependent Calcium Channels at the Plasma Membrane, but Not Vesicular Channels, Couple Exocytosis to Endocytosis, Cell reports 1(6), 632¨C638. Full Text/Abstract

  • Sun T, Wu XS, Xu J, McNeil BD, Pang ZP, Yang W, Bai L, Qadri S, Molkentin JD, Yue DT, Wu LG. (2010) The role of calcium/calmodulin-activated calcineurin in rapid and slow endocytosis at central synapses., Journal of Neuroscience. 30(35):, 11838-47. Full Text/Abstract

  • Wu XS, McNeil BD, Xu J, Fan J, Xue L, Melicoff E, Adachi R, Bai L, Wu LG (2009) Ca(2+) and calmodulin initiate all forms of endocytosis during depolarization at a nerve terminal, Nat Neurosci. 12(8), 1003-10. Full Text/Abstract

  • He L, Xue L, Xu J, McNell B, Bai L, Melicoff E, Adachi R and Wu LG. (2009) Compound vesicle fusion increases quantal size and potentiates synaptic transmission, Nature 459, 93-98. Full Text/Abstract

  • Xu J, McNeil B, Wu W, Nees D, Bai L, Wu LG. (2008) GTP-independent rapid and slow endocytosis at a central synapse, Nat Neurosci. 11(1), 45-53. Full Text/Abstract

All Selected Publications


Contact Information:

Dr. Ling-Gang Wu
Synaptic Transmission Section, NINDS
Porter Neuroscience Research Center
Building 35, Room 2B-1012
35 Convent Drive, MSC 3706
Bethesda, MD 20892-3706

Telephone: (301) 451-3338 (office), (301) 451-3338 (laboratory), (301) 480-1466 (fax)
Email: wul@ninds.nih.gov

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