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Spatially regulated β-actin translation in epithelia

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TitleInfo
Title
Spatially regulated β-actin translation in epithelia
SubTitle
analysis of adherens junction assembly, membrane cytoskeletal dynamics and tissue function
Name (type = personal)
NamePart (type = family)
Vedula
NamePart (type = given)
Pavan
NamePart (type = date)
1988-
DisplayForm
Pavan Vedula
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Weber
NamePart (type = given)
Gregory F
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Gregory F Weber
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Advisory Committee
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chair
Name (type = personal)
NamePart (type = family)
Rodriguez
NamePart (type = given)
Alexis J
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Alexis J Rodriguez
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Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Gao
NamePart (type = given)
Nan
DisplayForm
Nan Gao
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Bonder
NamePart (type = given)
Edward M
DisplayForm
Edward M Bonder
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Hinchcliffe
NamePart (type = given)
Edward
DisplayForm
Edward Hinchcliffe
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
outside member
Name (type = personal)
NamePart (type = family)
Hinchcliffe
NamePart (type = given)
Edward H
DisplayForm
Edward H Hinchcliffe
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
outside member
Name (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (type = corporate)
NamePart
Graduate School - Newark
Role
RoleTerm (authority = RULIB)
school
TypeOfResource
Text
Genre (authority = marcgt)
theses
OriginInfo
DateCreated (qualifier = exact)
2016
DateOther (qualifier = exact); (type = degree)
2016-05
CopyrightDate (encoding = w3cdtf); (qualifier = exact)
2016
Place
PlaceTerm (type = code)
xx
Language
LanguageTerm (authority = ISO639-2b); (type = code)
eng
Abstract (type = abstract)
The β-actin mRNA contains a 28 nucleotide sequence in the 3′UTR termed the zipcode which, along with a trans acting factor called the Zipcode Binding Protein-1 (ZBP-1/IMP-1), regulates the spatio-temporal expression pattern of the β-actin. This mode of post-transcriptional gene regulation is required for several cellular processes including cell migration, cell-cell adhesion, and cell-matrix adhesion. Adding to the list of signaling cascades such as RhoA and Src, work in this thesis demonstrates E-cadherin endocytosis, and plausibly gene expression pathways regulating cell proliferation, converge on spatially regulated β-actin translation. E-cadherin endocytosis and recycling has been shown to be important during the maintenance of epithelial adherens junctions. However in this thesis, endocytosis of E-cadherin is shown to negatively regulate adherens junction assembly, while spatially regulated β-actin translation balances this by promoting actin filament anchoring of cadherin complexes. Mislocalization of β-actin translation impairs adherens junction maturation in epithelial cells following de novo cell-cell contact. These results have implications in development and disease where the assembly and maintenance of epithelial adherens junctions is essential. In order to quantify the extent of adherens junction assembly defects in epithelial cells following de novo contact, a Fluorescence Covariance Index based on calculating Pearson’s Correlation Coefficients was developed and validated using several components of the adherens junction complex. In addition to quantitating the morphological effects of mislocalizing β-actin translation on adherens junctions, the FCI analysis showed correlation of these morphological defects with loss of epithelial barrier function. Lastly, inhibiting dynamin mediated endocytosis rescued adherens junction structure and epithelial barrier function in cells with partially mislocalized β-actin. Using Matrigel embedded 3D cyst cultures of MDCK cells, spatially regulated β-actin translation was shown to have an effect on cell shape, size and proliferation during epithelial morphogenesis. These defects in assembling a normal 3D epithelium along with disorganized acto-myosin and tight junctions, point to a role for compartmentalized β-actin translation in regulating a mechanosensitive module – plausibly Hippo and/or YAP/TAZ pathways. Finally, collective cell migration, an important paradigm in several biological processes such as wound repair and development, was used to determine the role of spatially regulated β-actin translation in epithelial wound repair. Spatially regulated β-actin translation is shown to regulate actin flux at cell-cell adhesions in leader-follower cell pairs to control tissue migration rates. Although cells with partially mislocalized β-actin translation have a more active leading edge, this increased protrusive activity fails to translate into increased migratory rate. These data taken together suggest that collective cell migration in epithelial sheets is an emergent property of both single cell dynamics and cell-cell interactions.
Subject (authority = RUETD)
Topic
Biology
Subject (authority = ETD-LCSH)
Topic
Cell adhesion molecules
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_7365
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
1 online resource (xviii, 241 p. : ill.)
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = statement of responsibility)
by Pavan Vedula
RelatedItem (type = host)
TitleInfo
Title
Graduate School - Newark Electronic Theses and Dissertations
Identifier (type = local)
rucore10002600001
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier (type = doi)
doi:10.7282/T3K939QR
Genre (authority = ExL-Esploro)
ETD doctoral
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Rights

RightsDeclaration (ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Vedula
GivenName
Pavan
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2016-05-01 21:20:50
AssociatedEntity
Name
Pavan Vedula
Role
Copyright holder
Affiliation
Rutgers University. Graduate School - Newark
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

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2016-05-04T21:49:28
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2016-05-04T21:49:28
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