자료유형  

 학위논문

Control Number  

0017163254

International Standard Book Number  

9798383564707

Dewey Decimal Classification Number  

574.191

Main Entry-Personal Name  

Wu, Lanxi.

Publication, Distribution, etc. (Imprint  

[S.l.] : The University of Wisconsin - Madison., 2024

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2024

Physical Description  

174 p.

General Note  

Source: Dissertations Abstracts International, Volume: 86-01, Section: B.

General Note  

Advisor: Chapman, Edwin.

Dissertation Note  

Thesis (Ph.D.)--The University of Wisconsin - Madison, 2024.

Summary, Etc.  

요약Synaptic vesicle exocytosis results neurotransmitter release and is mainly mediated by soluble N-ethylmaleimide sensitive factor attachment protein receptors as the core fusion proteins with additional proteins and lipid molecules playing key roles in the fusion pathway. Fusion pore is the first crucial and short-lived intermediate in this pathway. Studying the dynamics and structure of the fusion pore is fundamental and crucial to understanding the mechanisms of exocytosis and neurotransmission. Recently developed technique combined nanodisc technology and black-lipid-membrane electrophysiology (ND-BLM system). The small sized NDs restrict the dilation of the fusion pore, and the BLM system allows a fast-sampling rate for measuring fusion pore activities at a single pore level. This dissertation focuses on using the ND-BLM system to study molecular factors that regulate fusion pore properties. Chapter II of this dissertation focused on a lipid molecule, cholesterol, which has been reported to affect SNARE-mediated exocytosis and fusion pore dynamic. Using the ND-BLM system, cholesterol is shown to significantly stabilize the fusion pore at the open state. Further study shows that these effects are attributed to the known role of cholesterol that alters membrane bending rigidity via the manipulation of unsaturated acyl-chains of phospholipids. To conclude, Chapter II shows that cholesterol stabilizes the fusion pore at the open state via modulating membrane bending rigidity. Chapter III focuses on a fusion accessory protein, complexin (Cpx). The C-terminal amphipathic helix of mammalian Cpx II forms pores on the membrane as well as budding vesicles from the membrane. In the ND-BLM system, this C-terminal amphipathic helix is shown to influence both the structure and the dynamics of the fusion pore. With these observations, Chapter III concludes that the membrane remodeling activity of Cpx promotes the recombinant fusion pore to open and then stabilize at the open state. After some efforts in understanding the molecular mechanism the regulation of the fusion pores, Chapter IV, future direction, continues to study the fusion pore dilation. Large sized NDs are used to allow further dilation of the fusion pore. The study of pore dilation will provide information about the regulation between kiss-and-run exocytosis and full-collapse exocytosis.

Subject Added Entry-Topical Term  

Biophysics.

Subject Added Entry-Topical Term  

Neurosciences.

Subject Added Entry-Topical Term  

Physiology.

Subject Added Entry-Topical Term  

Biochemistry.

Index Term-Uncontrolled  

Cholesterol

Index Term-Uncontrolled  

Complexin

Index Term-Uncontrolled  

Exocytosis

Index Term-Uncontrolled  

Fusion pores

Index Term-Uncontrolled  

Membrane fusion

Added Entry-Corporate Name  

The University of Wisconsin - Madison Biophysics

Host Item Entry  

Dissertations Abstracts International. 86-01B.

Electronic Location and Access  

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Control Number  

joongbu:654548