Presenting: Dr Zhitao Hu, UQ and Dr Fengfeng Niu, SUSTech
Hosted by: Professor Pankaj Sah & Professor Shengtao Hou
Date: Friday, August 27 2021
Time: 12PM (noon) – 1PM Shenzhen // 2PM – 3PM Brisbane


Meet the speakers

Dr Zhitao Hu

Senior Research Fellow and Group Leader, Queensland Brain Institute, The University of Queensland

Title: “A novel dual Ca2+ sensor system regulates Ca2+-dependent neurotransmitter release”

Abstract: Ca2+-dependent neurotransmitter release requires synaptotagmins as Ca2+ sensors to trigger synaptic vesicle (SV) exocytosis through binding of their tandem C2 domains (C2A and C2B) to Ca2+. We have previously demonstrated that SNT-1, a mouse synaptotagmin-1 (Syt1) homolog, functions as the fast Ca2+ sensor in C. elegans. Here we report a new Ca2+ sensor, SNT-3, which triggers delayed Ca2+-dependent neurotransmitter release. snt-1;snt-3 double mutants abolish evoked synaptic transmission, demonstrating that C. elegans NMJs use a dual Ca2+ sensor system. SNT-3 possesses canonical aspartate residues in both C2 domains, but lacks an N-terminal transmembrane (TM) domain. Biochemical evidence demonstrates that SNT-3 binds both Ca2+ and the plasma membrane. Functional analysis shows that SNT-3 is activated when SNT-1 function is impaired, triggering SV release that is loosely coupled to Ca2+ entry. Compared to SNT-1 which is tethered to SVs, SNT-3 is not SV associated. Eliminating the SV tethering of SNT-1 by removing the TM domain or the whole N terminus rescues fast release kinetics demonstrating that cytoplasmic SNT-1 is still functional and triggers fast neurotransmitter release, but exhibits decreased evoked amplitude and release probability. These results suggest that the fast and slow properties of SV release are determined by the intrinsically different C2 domains in SNT-1 and SNT-3, rather than their N termini-mediated membrane tethering. Our findings therefore reveal a novel dual-Ca2+ sensor system in C. elegans and provide significant insights into Ca2+-regulated exocytosis.


Dr Fengfeng Niu

Research Assistant Professor, Professor Zhiyi Wei’s Research Group, Southern University of Science and Technology

Title: “Competitive Binding of Mutually Antagonistic F-Actin Track Regulators to Myosin V Mediates Cargo Unloading”

Abstract: Intracellular cargo trafficking plays fundamental roles in normal cellular functions. Especially in neurons, the largely amplified trafficking is strictly regulated to ensure accurate positioning of diverse cargoes at proper locations. Myosin Va (MyoVa), an actin-based molecular motor, is a classic model for studying cargo transport. However, the molecular basis underlying cargo unloading in MyoVa-mediated transport has remained enigmatic. Here, we firstly identified MICAL1, an F-actin disassembly regulator, as a novel binding partner of MyoVa. In HeLa cells, we further confirmed that MICAL1-MyoVa interaction is critical for localization of MyoVa at the midbody. Furthermore, by binding to MICAL1, MyoVa-mediated transport is terminated, resulting in vesicle accumulation at the midbody for efficient cytokinesis. Interestingly, the MyoVa/MICAL1 complex structure reveals that MICAL1 and Spires, which are mutually antagonistic with MICAL1 as F-actin assembly factors, share an overlapped binding site on MyoVa, suggesting a regulatory role of F-actin dynamics in MyoVa-mediated cargo unloading. Consistently, down-regulating F-actin disassembly by a MICAL1 catalytically inactive mutant significantly reduces MyoVa and vesicles accumulating at the midbody. Collectively, MyoVa competitively binds to MICAL1 and triggers F-actin track disassembly to terminate the transportation and unload the cargoes at the destination. Our findings not only provide a molecular linkage between actin dynamics and cargo transport, but also uncover a novel cargo unloading mechanism for the molecular motor-mediated intracellular cargo trafficking.

About CNNE Program

The CNNE Program and Seminar Series provides a forum for SUSTech and QBI members to showcase collaboration in key thematic areas and foster new projects.

All are welcome to join this meeting via ZOOM.