MBGE SEMINAR by Erdem Karatekin

Time: 14:30
Location: SCI 103

Speaker          :
Dr. Erdem Karatekin, Yale University

Title                : Role of fusion pore dynamics and pre-synaptic membrane mechanics in neurotransmitter and hormone release

Date                : July 16, 2019, Tuesday
Time               : 14:30   
Cookie & Tea: 14:15 SCI 103 
Place               : SCI 103  

Abstract         :

Calcium-triggered release of neurotransmitters and hormones underlie neuronal communication and physiological regulation. Cargo release requires expansion of the initial, nanometer-sized fusion pore connecting a cargo-laden vesicle and the cell membrane. Pore dynamics contribute to release kinetics and determine the mode of vesicle recycling, but mechanisms are poorly understood. We developed an approach to monitor single fusion pores with biochemically defined components to characterize such mechanisms. Release requires neuronal/exocytic v- and t-SNARE proteins to form complexes bridging the fusing membranes. We fuse nanodiscs reconstituted with v-SNARE proteins with engineered cells expressing cognate t-SNAREs in a flipped topology. Fusion results in a pore that connects the cytoplasm to the exterior, allowing single-pore conductance measurements under voltage-clamp. We found pore formation requires only a few SNARE complexes, but pore expansion relies on many more. The calcium-sensor Synaptotagmin-1 contributes to pore expansion using the SNARE complex as a calcium-dependent lever.

Another important factor regulating synaptic transmission and hormone release is membrane tension. Increased tension promotes fusion pore dilation and strongly inhibits endocytosis, while decreased tension leads to transient pores and facilitates endocytosis. It has been proposed that a reduction in tension due to exocytic membrane addition to the presynaptic terminal surface could provide a mechanism that couples exo- and endocytosis. Such a coupling implies membrane flow from an exocytic site to an endocytic one, but such flows have never been demonstrated, and so the relationship between synaptic vesicle and tension dynamics is unknown. Using optical tweezers to pull thin membrane tethers from pre-synaptic membranes, we show that membrane flow and tension equilibration at the presynaptic plasma membrane is exceptionally facile, likely tuned for rapid turnover of synaptic vesicles.


1999 Ph.D., with Distinction (Chemistry). Columbia University, New York.

1996 M. S. (Chemistry). Columbia University, New York.

1994 B. S. (Chemical Engineering, with Highest Honors. Minor in Physics). University of Louisville, Kentucky.

2018- Associate Professor on term, Department of Cellular & Molecular Physiology, School of Medicine, Yale University