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Contact localized β-actin translation drives epithelial adherens junction assembly

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TitleInfo
Title
Contact localized β-actin translation drives epithelial adherens junction assembly
Name (type = personal)
NamePart (type = family)
Gutierrez
NamePart (type = given)
Natasha C.
NamePart (type = date)
1987-
DisplayForm
Natasha C. Gutierrez
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Rodriguez
NamePart (type = given)
Alexis
DisplayForm
Alexis Rodriguez
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
chair
Name (type = personal)
NamePart (type = family)
Bonder
NamePart (type = given)
Edward
DisplayForm
Edward Bonder
Affiliation
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)
Larson
NamePart (type = given)
Daniel
DisplayForm
Daniel Larson
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)
2014
DateOther (qualifier = exact); (type = degree)
2014-10
CopyrightDate (encoding = w3cdtf)
2014
Place
PlaceTerm (type = code)
xx
Language
LanguageTerm (authority = ISO639-2b); (type = code)
eng
Abstract (type = abstract)
Adherens junctions are multi-protein adhesion complexes that anchor to the actin cytoskeleton at cell-cell contact sites to stimulate tissue assembly and thereby regulate barrier maintenance, epithelial tissue homeostasis, and embryonic development. Previously it was demonstrated that the mRNA for β-actin contains a nucleotide sequence in its 3’ UTR, called the zipcode, which is necessary for targeting and translational regulation of this transcript. The zipcode sequence is recognized by the translation regulator zipcode binding protein-1, ZBP1. Additionally, deleting zipcode sequences causes mislocalization of their mRNA transcript. Here we show mislocalizing β-actin’s monomer synthesis inhibits adherens junction assembly following epithelial cell-cell contact. Additionally, inhibiting RhoA and Src signaling, required for β-actin mRNA zipcode-mediated spatially regulated β-actin translation, prevents adherens junction assembly and significantly perturbs epithelial barrier integrity. In fact, TRITC-dextran barrier permeability significantly increases in epithelial cells expressing β-actin transcripts without the 3’ untranslated region (Δ3’UTR-β-actin) at steady state and in the hours post-contact compared to full-length expressing cells. Moreover, in full-length β-actin GFP (FL-β-actin GFP) expressing cells, β-actin mRNA zipcode antisense oligonucleotide masking of the zipcode sequence also perturbs barrier maintenance. Intriguingly, chemically inhibiting the signaling pathways required for β-actin mRNA localization and local translation (RhoA and Src) also perturbs epithelial barrier maintenance. Taken together, we demonstrate epithelial cell-cell contact stimulates E-cadherin mediated signaling to spatially regulate β-actin mRNA zipcode-dependent monomer synthesis thereby driving adherens junction assembly, cell, and tissue adhesion required for proper epithelial tissue function.
Subject (authority = RUETD)
Topic
Biology
Subject (authority = ETD-LCSH)
Topic
Actin
Subject (authority = ETD-LCSH)
Topic
Cell adhesion molecules
Subject (authority = ETD-LCSH)
Topic
Cell receptors
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_5820
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
1 online resource (xvi, 200 p. : ill.)
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = vita)
Includes vita
Note (type = statement of responsibility)
Natasha C. Gutierrez
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/T37S7QDX
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
Gutierrez
GivenName
Natasha
MiddleName
C.
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2014-09-09 15:12:04
AssociatedEntity
Name
Natasha Gutierrez
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

RULTechMD (ID = TECHNICAL1)
ContentModel
ETD
OperatingSystem (VERSION = 5.1)
windows xp
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