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The role and regulation of an actomyosin complex in membrane remodeling during regulated exocytosis in a live rodent model system
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TitleInfo
Title
The role and regulation of an actomyosin complex in membrane remodeling during regulated exocytosis in a live rodent model system
Name
(type = personal)
NamePart
(type = family)
Milberg
NamePart
(type = given)
Oleg
NamePart
(type = date)
1983-
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Oleg Milberg
Role
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(authority = RULIB)
author
Name
(type = personal)
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(type = family)
Yarmush
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(type = given)
Martin
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Martin Yarmush
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Advisory Committee
Role
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(authority = RULIB)
chair
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(type = family)
Sofou
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Stavroula
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Stavroula Sofou
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Advisory Committee
Role
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(authority = RULIB)
internal member
Name
(type = personal)
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(type = family)
Roth
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(type = given)
Charlie
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Charlie Roth
Affiliation
Advisory Committee
Role
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(authority = RULIB)
internal member
Name
(type = personal)
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(type = family)
Grant
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(type = given)
Barth
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Barth Grant
Affiliation
Advisory Committee
Role
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(authority = RULIB)
outside member
Name
(type = personal)
NamePart
(type = family)
Donaldson
NamePart
(type = given)
Julie
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Julie Donaldson
Affiliation
Advisory Committee
Role
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(authority = RULIB)
outside member
Name
(type = personal)
NamePart
(type = family)
Weigert
NamePart
(type = given)
Roberto
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Roberto Weigert
Affiliation
Advisory Committee
Role
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(authority = RULIB)
outside member
Name
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NamePart
Rutgers University
Role
RoleTerm
(authority = RULIB)
degree grantor
Name
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NamePart
Graduate School - New Brunswick
Role
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school
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Text
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theses
OriginInfo
DateCreated
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2015
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(type = degree)
2015-10
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2015
Place
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(type = code)
xx
Language
LanguageTerm
(authority = ISO639-2b);
(type = code)
eng
Abstract
(type = abstract)
Our lab has developed a subcellular imaging technique based on intravital microscopy (IVM) to study the highly conserved process of regulated exocytosis, as it occurs in live rodents, using the submandibular salivary glands (SSGs) as a model system for exocrine secretion. Previous work, mainly done on rats and commercially available transgenic and wild-type mice, determined that an actomyosin complex, composed of F-actin and nonmuscle myosin II (NMII) isoforms A and B (NMIIA and NMIIB, respectively), forms around single secretory granules that have fused with the apical plasma membrane (APM) following β-adrenergic stimulation of regulated exocytosis. This complex is required to promote the full integration of the granules into the APM, and although the role of F-actin in regulating granule integration was established, the roles and regulation of NMIIA and NMIIB in this process were not determined, and therefore, they are the main topics discussed in this thesis. To this end, a series of tools, which includes 1) NMII floxed mice, 2) transgenic and knock-in mice, 3) transgene delivery and expression by viral and non-viral means, and 4) various pharmacological inhibition approaches, were developed. This thesis work shows that: 1) both NMII isoforms are required for granule integration to occur, with NMIIA regulating the dynamics of the fusion pore and NMIIB stabilizing the granules and providing the necessary force for their gradual integration; 2) both NMII isoforms are recruited onto the granules in an F-actin independent manner and subsequently activated by the phosphorylation of their regulatory light chains by myosin light chain kinase (MLCK); and 3) MLCK is recruited through the GTPase Septin 2, and possibly other members of the septin family (Septins 6, 7 and 9) in an F-actin dependent manner. Live imaging by IVM provided further details on the kinetics and dynamics of actomyosin complex assembly and function, which lead to a mechanistic model of actomyosin activity in membrane remodeling during regulated exocytosis in the SSGs. This work is the first to describe how the actomyosin complex functions in a live rodent during a normal physiological process.
Subject
(authority = RUETD)
Topic
Chemical and Biochemical Engineering
RelatedItem
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TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier
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ETD
Identifier
ETD_6723
PhysicalDescription
Form
(authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
1 online resource (xiv, 183 p. : ill.)
Note
(type = degree)
Ph.D.
Note
(type = bibliography)
Includes bibliographical references
Subject
(authority = ETD-LCSH)
Topic
Exocytosis
Subject
(authority = ETD-LCSH)
Topic
Cell membranes
Note
(type = statement of responsibility)
by Oleg Milberg
RelatedItem
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TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier
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rucore19991600001
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(displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier
(type = doi)
doi:10.7282/T3R49SSJ
Genre
(authority = ExL-Esploro)
ETD doctoral
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Rights
RightsDeclaration
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The author owns the copyright to this work.
RightsHolder
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Name
FamilyName
Milberg
GivenName
Oleg
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime
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(qualifier = exact);
(point = start)
2015-09-10 12:09:48
AssociatedEntity
Name
Oleg Milberg
Role
Copyright holder
Affiliation
Rutgers University. Graduate School - New Brunswick
AssociatedObject
Type
License
Name
Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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Technical
RULTechMD
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ContentModel
ETD
OperatingSystem
(VERSION = 5.1)
windows xp
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