Neurons contact each other mostly by synaptic transmission at synapses. Synaptic transmission relies on vesicle exocytosis, i.e., fusion of vesicles with the plasma membrane and release of transmission. To maintain vesicle exocytosis, fused vesicles must be retrieved, or endocytosed, to form new vesicles for the second round of exocytosis. My goal is to improve our understanding on the cellular and molecular mechanisms underlying synaptic vesicle exocytosis and endocytosis, which are the building block for synaptic transmission and thus the signaling process in the neuronal network. ? ? My progress in the last year is listed in the following. First, we found two modes of fusion, full collapse and kiss and run mode (Nature, 2006). The kiss-and-run mode may release transmitter slowly depending on its fusion pore size, and thus provide a method to control synatic strength. Second, we found that quantal size, the most fundamental parameter that determines synaptic strength, is regulated by the glutamate concentration inside the vesicle (J Neurosci, 2007). Third, we resolved the final step of the bulk endocytosis, the fission process, and provided the first measurement of the fission rate at synapses (PNAS, 2007).

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Intramural Research (Z01)
Project #
1Z01NS003009-04
Application #
7594701
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2007
Total Cost
$2,495,590
Indirect Cost
City
State
Country
United States
Zip Code
He, Liming; Wu, Ling-Gang (2007) The debate on the kiss-and-run fusion at synapses. Trends Neurosci 30:447-55
Wu, Ling-Gang; Ryan, Timothy A; Lagnado, Leon (2007) Modes of vesicle retrieval at ribbon synapses, calyx-type synapses, and small central synapses. J Neurosci 27:11793-802
He, Liming; Wu, Xin-Sheng; Mohan, Raja et al. (2006) Two modes of fusion pore opening revealed by cell-attached recordings at a synapse. Nature 444:102-5
Xu, Jianhua; Wu, Ling-Gang (2005) The decrease in the presynaptic calcium current is a major cause of short-term depression at a calyx-type synapse. Neuron 46:633-45
Wu, Wei; Xu, Jianhua; Wu, Xin-Sheng et al. (2005) Activity-dependent acceleration of endocytosis at a central synapse. J Neurosci 25:11676-83