Meet the Team
Weichun Lin, Ph.D.
Effie Marie Cain Scholar in Medical Research
Department of Neuroscience
Dr. Lin obtained his Ph.D. in Neurobiology from the State University of New York at Albany in 1996. He then moved to the Salk Institute at La Jolla, Calif., as a postdoctoral fellow and research associate. He joined the faculty at the Department of Neuroscience in 2003. His research interest focuses on cellular and molecular basis of synapse formation, function, maintenance, and degeneration, using approaches including electrophysiology, genetics, and molecular biology.
Current Lab Members
Past Lab Members
- Peter Alexander - rotation grad student
- Jie Cao, Ph.D. - Rutgers University, New Jersey
- Fujun Chen, Ph.D. - East China Normal University, China
- Harry Hongqiao Li, Ph.D. - Max Planck Institute/Philipps University, Marburg, Germany
- Courtney Karner - rotation grad student
- Xue Li, Ph.D. - University of Tokyo, Tokyo, Japan
- David Philopateer Mikhail - Green Fellow
- Kalisa Myers, M.S.
- Lisa O’Connor - High School Star Teacher
- Daniel Padgett, M.S.
- Marco Perez - SURF Student
- Jennifer Putman - rotation grad student
- Ayesha Shafi - SURF Student
- Yoshie Sugiura, Ph.D. - Tokyo Medical & Dental University, Tokyo, Japan
- Thi Tran - rotation grad student
- Katherine Wasser - rotation grad student
- Hongyi Zhang - High School Student
The human brain contains over 100 billion neurons inter-connected through specialized cell-cell contacts termed synapses. Synaptic connections, estimated to be around 100 trillion in number, form intricate networks that enable neurons to send and receive information and generate complex behavior. The goal of our research is to understand how neurons establish synaptic connections during development, and how these connections are maintained throughout adulthood. Toward this goal, we are currently focusing on the following two areas of research.
Patterning and Formation of Synapses
Formation of synapses lays the foundation for neural circuits. We study the vertebrate neuromuscular junction (NMJ) to understand the cellular and molecular mechanisms of synaptogenesis. At the developing NMJ, the nerve terminals progressively accumulate synaptic proteins and form synapses within a discrete area often localized to the central region of the muscle. One of the questions that we are particularly interested in is identifying signaling molecules that determine the spatial pattern of synaptic organization of the NMJ. We are investigating several mutant mice in which the NMJ pattern is disrupted due to specific mutations. This will allow us to define the roles of specific molecules in determining the patterning and formation of synapses.
Molecular Mechanisms of Neurodegeneration
Impairments of synapses are implicated in the pathogeneses of various neurodegenerative diseases, including Alzheimer’s disease and amyotrophic lateral sclerosis (Lou Gehrig's disease). Indeed, synaptic dysfunction may be the earliest sign of neurodegeneration, but little is known about why normal synapses may degenerate. We have generated a transgenic mouse model in which synapses form normally during development, but become progressively dysfunctional and eventually degenerate. We are studying these transgenic mice to gain a better understanding of the mechanisms underlying synaptic dysfunction and degeneration.
Original Research Articles
Yun Liu and Weichun Lin (2022) Structural and functional alterations of neuromuscular synapses in a mouse model of ACTA1 congenital myopathy. bioRxiv 481672.
Yun Liu and Weichun Lin (2022) Genetic deletion of Kiaa1109 in mice leads to developmental defects at the neuromuscular junction. bioRxiv 482678.
Yun Liu, Yoshie Sugiura, Fujun Chen, Kuo-Fen Lee, Qiaohong Ye and Weichun Lin (2019). Blocking skeletal muscle DHPRs/Ryr1 prevents neuromuscular synapse loss in type III Neuregulin 1 (CRD-Nrg1) mutant mice. PLOS Genetics 15(3): e1007857. doi: 10.1371/journal.pgen.1007857. PubMed PMID: 30870432; PubMed Central PMCID: PMC6417856.
Thomas W Gould, Bertha Dominguez, Fred de Winter, Gene W. Yeo, Patrick Liu, Balaji Sundaraman, Thomas Stark, Anthony Vu, Jay L. Degen, Weichun Lin and Kuo-Fen Lee (2019). Glial cells maintain synapses by inhibiting an activity-induced retrograde protease signal. PLOS Genetics 15(3): e1007948. doi: 10.1371/journal.pgen.1007948. PubMed PMID: 30870413; PubMed Central PMCID: PMC6417855.
Yun Liu, Yoshie Sugiura, Thomas C. Südhof and Weichun Lin (2019) Ablation of all synaptobrevin vSNAREs blocks evoked but not spontaneous neurotransmitter release at neuromuscular synapses. The Journal of Neuroscience, 39: 6049-6066 PMID: 31160536 PMCID: PMC6668203.
Yun Liu, Hongqiao Li, Yoshie Sugiura, Gilbert Gallardo, Mikhail Khvotchev, Weiping Han, Thomas C. Südhof and Weichun Lin (2015) Ubiquitin-Synaptobrevin fusion protein causes degeneration of presynaptic motor terminals in mice. Journal of Neuroscience 35 (33):11514-11531. PMID: 26290230
Choi HY, Liu Y, Tennert C, Sugiura Y, Karakatsani A, Kröger S, Johnson EB, Hammer RE, Lin W, Herz J. APP interacts with LRP4 and agrin to coordinate the development of the neuromuscular junction in mice. Elife. 2013 Aug 20;2:e00220. doi: 10.7554/eLife.00220. PubMed PMID: 23986861.
Yun Liu, Yoshie Sugiura, Fenfen Wu, Wentao Mi, Makoto M. Taketo, Steve Cannon, Thomas Carroll, and Weichun Lin (2012) β-Catenin stabilization in skeletal muscles, but not in motor neurons, leads to aberrant motor innervation of the muscle during neuromuscular development in mice. Developmental Biology, 366:255-267. PMID: 22537499
Fujun Chen, Yun Liu, Yoshie Sugiura, Paul D. Allen, Ronald G. Gregg, and Weichun Lin (2011) Neuromuscular synaptic patterning requires the function of skeletal muscle dihydropyridine receptors. Nat Neurosci. 14(5):570-7.
Yun Liu, Yoshie Sugiura, and Weichun Lin (2011) The role of Synaptobrevin-1/VAMP-1 in Ca2 -triggered synaptic transmission at the mouse NMJ. J Physiol. 589:1603-18.
Mahru An, Weichun Lin, Jiefei Yang, Bertha Dominguez, Daniel Padgett, Yoshie Sugiura, Prafulla Aryal, Thomas W. Gould, Ronald W. Oppenheim, Mark Hester, Brian Kasper, Chien-Ping Ko, and Kuo-Fen Lee (2010) Acetylcholine negatively regulates development of the neuromuscular junction through distinct cellular mechanisms. Proceedings of the National Academy of Sciences, U.S.A. 107:10702-7.
Fujun Chen, Yoshie Sugiura, Kalisa Galina Myers, Yun Liu, and Weichun Lin (2010) Ubiquitin carboxyl-terminal hydrolase L1 is required for maintaining the structure and function of the neuromuscular junction. Proceedings of the National Academy of Sciences, U.S.A. 107:1636-1641.
Yun Liu, Yoshie Sugiura, Daniel Padgett, and Weichun Lin (2010) Post-synaptic development of the neuromuscular junction in mice lacking the gamma-subunit of muscle nicotinic acetylcholine receptor. Journal of Molecular Neuroscience, 40: 21-26.
Yun Liu, Oppenheim, R. W., Sugiura, Y., and Weichun Lin (2009) Abnormal development of the neuromuscular junction in Nedd4-deficient mice. Developmental Biology, 330:153-166.
Yun Liu, Daniel Padgett, Masazumi Takahashi, Hongqiao Li, Ayaz Sayeed, Russell W. Teichert, Baldomero M. Olivera, Joseph McArdle, William N. Green, and Weichun Lin (2008) Essential roles of acetylcholine receptor gamma-subunit in neuromuscular synaptic patterning. Development, 135:1957-1967.
Zhiping Pang, Ernestina Melicoff, Daniel Padgett, Yun Liu, Andrew F. Teich, Burton F. Dickey, Weichun Lin, Roberto Adachi, and Thomas Sudhof (2006) Synaptotagmin-2 is essential for survival and contributes to Ca2 triggering of neurotransmitter release in central and neuromuscular synapses. Journal of Neuroscience, 26:13493-13504.
Susanne Schoch, Tobias Mittelstaedt, Pascal S. Kaeser, Daniel Padgett, Nicole Feldmann, Vivien Cgeveleyre, Pablo E. Cassillo, Robert Hammer, Weiping Han, Frank Schmitz, Weichun Lin, and Thomas Sudhof (2006) Redundant functions of RIM1-alpha and RIM2-alpha in Calcium triggered neurotransmitter release. EMBO Journal, 25:5852-5863.
Weiping Han, Jeong-Seop Rhee, Anton Maximov, Weichun Lin, Robert Hammer, Christian Rosenmund and Thomas Sudhof (2005) C-terminal ECFP fusion impairs synaptotagmin-1 function: crowding out synaptotagmin1. J Biol Chem, 280:5089-5100.
Weichun Lin, Bertha Dominguez, Jiefei Yang, Prafulla Aryal, Eugene P. Brandon, Fred H. Gage, and Kuo-Fen Lee (2005) Neurotransmitter acetylcholine negatively regulates. Neuromuscular synapse formation through a Cdk5-dependent mechanism. Neuron, 46:569-579.
Eugene P. Brandon*, Weichun Lin*, Kevin A. D'Amour, Donald P. Pizzo, Bertha Dominguez, Yoshie Sugiura, Sile Thode, Chien-Ping Ko, Leon J. Thal, Fred H. Gage, and Kuo-Fen Lee (2003) Aberrant patterning of neuromuscular synapses in choline acetyltransferase deficient mice. Journal of Neuroscience 23:539-549 *Co-first author
Weichun Lin, Robert Burgess, Bertha Dominguez, Samuel Pfaff, Joshua Sanes and Kuo-Fen Lee (2001) Distinct roles of nerve and muscle in postsynaptic differentiation of the neuromuscular synapse. Nature, 410:1057-1064.
Weichun Lin, Hugo Sanchez, Tom Deerinck, Jacqueline K. Morris, Mark Ellisam and Kuo-Fen Lee (2000) Abnormal development of motor axons and neuromuscular synapses in erbB2-deficient mice. Proceedings of the National Academy of Sciences, 97:1299-1304.
Jacqueline K. Morris*, Weichun Lin*, Chris Hauser, Yelena Marchuk, Damon Getman, and Kuo-Fen Lee (1999) Rescue of cardiac defect in erbB2 null mutant mice reveals essential roles of erbB2 in peripheral nervous system development. Neuron, 23:273-283. *Co-first author.
Yoshie Sugiura, Fujun Chen, Yun Liu and Weichun Lin (2011) Electrophysiological characterization of neuromuscular synaptic dysfunction in mice. In: Methods in Molecular Biology 793: 391-400. PMID: 21913115 PMCID: PMC4590777
Yoshie Sugiura and Weichun Lin (2011) Neuro-glia interaction: the role of Schwann cell in neuromuscular synapse formation and function. Bioscience Reports 31: 295-302 PMID: 21517783 PMCID: PMC4573580
Weichun Lin and Joseph J McArdle (2021) The NMJ as a model synapse: new perspectives on synapse formation, function and maintenance. Neuroscience Letters 740: 135431, PMID: 33086091, PMC8274589.