A role for synapsin 2a oligomerization in maintaining a reserve pool of synaptic vesicles

Although it is known that synapsins maintain a reserve pool (RP) of synaptic vesicles (SVs) within presynaptic terminals, the precise mechanism involved in this action remains elusive. I have tested the role of synapsin oligomerization in this process by examining the ability of an oligomerization-d...

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Main Author: Zhang, Minchuan
Other Authors: George Augustine
Format: Thesis-Doctor of Philosophy
Language:English
Published: Nanyang Technological University 2022
Subjects:
Online Access:https://hdl.handle.net/10356/159292
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author Zhang, Minchuan
author2 George Augustine
author_facet George Augustine
Zhang, Minchuan
author_sort Zhang, Minchuan
collection NTU
description Although it is known that synapsins maintain a reserve pool (RP) of synaptic vesicles (SVs) within presynaptic terminals, the precise mechanism involved in this action remains elusive. I have tested the role of synapsin oligomerization in this process by examining the ability of an oligomerization-deficient mutant of synapsin 2a to rescue the RP defects of cultured glutamatergic neurons from synapsin triple knock-out (TKO) mice. My results showed that the oligomerization-deficient synapsin 2a mutant was not able to rescue the defective RP size, impaired RP mobilization, and enhanced inter-bouton movement of SVs in TKO neurons. This differs from the effects of wild-type synapsin 2a, which can rescue all of these phenotypes. Therefore, the loss of oligomerization prevents synapsin 2a from maintaining the RP of SVs within presynaptic terminals. My results support the idea that oligomerization of synapsin 2a is important for maintaining glutamatergic SVs within the RP of presynaptic terminals, thereby providing a molecular explanation for how the RP can supply SVs during sustained synaptic activity.
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spelling ntu-10356/1592922023-03-05T17:10:03Z A role for synapsin 2a oligomerization in maintaining a reserve pool of synaptic vesicles Zhang, Minchuan George Augustine Lee Kong Chian School of Medicine (LKCMedicine) George.Augustine@ntu.edu.sg Science::Biological sciences::Molecular biology Although it is known that synapsins maintain a reserve pool (RP) of synaptic vesicles (SVs) within presynaptic terminals, the precise mechanism involved in this action remains elusive. I have tested the role of synapsin oligomerization in this process by examining the ability of an oligomerization-deficient mutant of synapsin 2a to rescue the RP defects of cultured glutamatergic neurons from synapsin triple knock-out (TKO) mice. My results showed that the oligomerization-deficient synapsin 2a mutant was not able to rescue the defective RP size, impaired RP mobilization, and enhanced inter-bouton movement of SVs in TKO neurons. This differs from the effects of wild-type synapsin 2a, which can rescue all of these phenotypes. Therefore, the loss of oligomerization prevents synapsin 2a from maintaining the RP of SVs within presynaptic terminals. My results support the idea that oligomerization of synapsin 2a is important for maintaining glutamatergic SVs within the RP of presynaptic terminals, thereby providing a molecular explanation for how the RP can supply SVs during sustained synaptic activity. Doctor of Philosophy 2022-06-14T05:12:24Z 2022-06-14T05:12:24Z 2022 Thesis-Doctor of Philosophy Zhang, M. (2022). A role for synapsin 2a oligomerization in maintaining a reserve pool of synaptic vesicles. Doctoral thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/159292 https://hdl.handle.net/10356/159292 en This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0). application/pdf Nanyang Technological University
spellingShingle Science::Biological sciences::Molecular biology
Zhang, Minchuan
A role for synapsin 2a oligomerization in maintaining a reserve pool of synaptic vesicles
title A role for synapsin 2a oligomerization in maintaining a reserve pool of synaptic vesicles
title_full A role for synapsin 2a oligomerization in maintaining a reserve pool of synaptic vesicles
title_fullStr A role for synapsin 2a oligomerization in maintaining a reserve pool of synaptic vesicles
title_full_unstemmed A role for synapsin 2a oligomerization in maintaining a reserve pool of synaptic vesicles
title_short A role for synapsin 2a oligomerization in maintaining a reserve pool of synaptic vesicles
title_sort role for synapsin 2a oligomerization in maintaining a reserve pool of synaptic vesicles
topic Science::Biological sciences::Molecular biology
url https://hdl.handle.net/10356/159292
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