Roles of cholesterol in vesicle fusion and motion

Although it is well established that exocytosis of neurotransmitters and hormones is highly regulated by numerous secretory proteins, such as SNARE proteins, there is an increasing appreciation of the importance of the chemophysical properties and organization of membrane lipids to various aspects o...

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Main Authors: Zhang, Jing, Xue, Renhao, Ong, Wei-Yi, Chen, Peng
Other Authors: School of Chemical and Biomedical Engineering
Format: Journal Article
Language:English
Published: 2012
Subjects:
Online Access:https://hdl.handle.net/10356/94314
http://hdl.handle.net/10220/7527
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author Zhang, Jing
Xue, Renhao
Ong, Wei-Yi
Chen, Peng
author2 School of Chemical and Biomedical Engineering
author_facet School of Chemical and Biomedical Engineering
Zhang, Jing
Xue, Renhao
Ong, Wei-Yi
Chen, Peng
author_sort Zhang, Jing
collection NTU
description Although it is well established that exocytosis of neurotransmitters and hormones is highly regulated by numerous secretory proteins, such as SNARE proteins, there is an increasing appreciation of the importance of the chemophysical properties and organization of membrane lipids to various aspects of the exocytotic program. Based on amperometric recordings by carbon fiber microelectrodes, we show that deprivation of membrane cholesterol by methyl-b-cyclodextrin not only inhibited the extent of membrane depolarization-induced exocytosis, it also adversely affected the kinetics and quantal size of vesicle fusion in neuroendocrine PC12 cells. In addition, total internal fluorescence microscopy studies revealed that cholesterol depletion impaired vesicle docking and trafficking, which are believed to correlate with the dynamics of exocytosis. Furthermore, we found that free cholesterol is able to directly trigger vesicle fusion, albeit with less potency and slower kinetics as compared to membrane depolarization stimulation. These results underscore the versatile roles of cholesterol in facilitating exocytosis.
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spelling ntu-10356/943142023-12-29T06:50:55Z Roles of cholesterol in vesicle fusion and motion Zhang, Jing Xue, Renhao Ong, Wei-Yi Chen, Peng School of Chemical and Biomedical Engineering DRNTU::Science::Medicine::Biomedical engineering Although it is well established that exocytosis of neurotransmitters and hormones is highly regulated by numerous secretory proteins, such as SNARE proteins, there is an increasing appreciation of the importance of the chemophysical properties and organization of membrane lipids to various aspects of the exocytotic program. Based on amperometric recordings by carbon fiber microelectrodes, we show that deprivation of membrane cholesterol by methyl-b-cyclodextrin not only inhibited the extent of membrane depolarization-induced exocytosis, it also adversely affected the kinetics and quantal size of vesicle fusion in neuroendocrine PC12 cells. In addition, total internal fluorescence microscopy studies revealed that cholesterol depletion impaired vesicle docking and trafficking, which are believed to correlate with the dynamics of exocytosis. Furthermore, we found that free cholesterol is able to directly trigger vesicle fusion, albeit with less potency and slower kinetics as compared to membrane depolarization stimulation. These results underscore the versatile roles of cholesterol in facilitating exocytosis. Accepted version 2012-02-21T01:09:19Z 2019-12-06T18:54:01Z 2012-02-21T01:09:19Z 2019-12-06T18:54:01Z 2009 2009 Journal Article Zhang, J., Xue, R., Ong, W. Y., & Chen, P. (2009). Roles of cholesterol in vesicle fusion and motion. Biophysical Journal, 97(5), 1371–1380. https://hdl.handle.net/10356/94314 http://hdl.handle.net/10220/7527 10.1016/j.bpj.2009.06.025 19720025 149064 en Biophysical journal © 2009 Biophysical Society. This is the author created version of a work that has been peer reviewed and accepted for publication by Biophysical journal, Biophysical Society. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: http://dx.doi.org/10.1016/j.bpj.2009.06.025. application/pdf
spellingShingle DRNTU::Science::Medicine::Biomedical engineering
Zhang, Jing
Xue, Renhao
Ong, Wei-Yi
Chen, Peng
Roles of cholesterol in vesicle fusion and motion
title Roles of cholesterol in vesicle fusion and motion
title_full Roles of cholesterol in vesicle fusion and motion
title_fullStr Roles of cholesterol in vesicle fusion and motion
title_full_unstemmed Roles of cholesterol in vesicle fusion and motion
title_short Roles of cholesterol in vesicle fusion and motion
title_sort roles of cholesterol in vesicle fusion and motion
topic DRNTU::Science::Medicine::Biomedical engineering
url https://hdl.handle.net/10356/94314
http://hdl.handle.net/10220/7527
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