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The role of NOS1AP, a schizophrenia susceptibility gene, in the regulation of dendrite branching, dendritic spine formation, and actin dynamics.
Descriptive
TitleInfo
Title
The role of NOS1AP, a schizophrenia susceptibility gene, in the regulation of dendrite branching, dendritic spine formation, and actin dynamics.
Name
(type = personal)
NamePart
(type = family)
Hernandez
NamePart
(type = given)
Kristina
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(type = date)
1985-
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Kristina Hernandez
Role
RoleTerm
(authority = RULIB)
author
Name
(type = personal)
NamePart
(type = family)
Firestein
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(type = given)
Bonnie L.
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Bonnie L. Firestein
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Advisory Committee
Role
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(authority = RULIB)
chair
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(type = family)
Tischfield
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(type = given)
Jay A.
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Jay A. Tischfield
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Advisory Committee
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(authority = RULIB)
internal member
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(type = personal)
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(type = family)
Moore
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(type = given)
Jennifer C.
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Jennifer C. Moore
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Advisory Committee
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internal member
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Hart
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(type = given)
Ronald P.
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Ronald P. Hart
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Advisory Committee
Role
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internal member
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(type = family)
Brzustowicz
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(type = given)
Linda M.
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Linda M. Brzustowicz
Affiliation
Advisory Committee
Role
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(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Silverstein
NamePart
(type = given)
Steve
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Steve Silverstein
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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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(qualifier = exact)
2015
DateOther
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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)
Proper communication between neurons is dependent upon the appropriate patterning of dendrites and the correct distribution and structure of spines. Schizophrenia is one of several neurodevelopmental disorders that are characterized by alterations in dendrite branching and spine density. NOS1AP is a protein encoded by a schizophrenia susceptibility gene, and its expression is upregulated in the dorsolateral prefrontal cortex of patients with schizophrenia. Previously, our laboratory showed that NOS1AP isoforms negatively regulate dendrite branching in cultured rat hippocampal neurons. Since dendrites and spines are influenced by changes in the cytoskeleton, we investigated whether the overexpression of NOS1AP isoforms in heterologous cells alters actin and microtubule organization. Overexpression of a long isoform of NOS1AP (NOS1AP-L) increases the presence of microtubule organizing centers, whereas overexpression of the short isoform of NOS1AP (NOS1AP-S) decreases microtubule organization. Furthermore, NOS1AP isoforms associate with F-actin in rat brain and can alter actin organization in distinct ways. NOS1AP-S increases actin polymerization, and its overexpression in HEK293T cells decreases total Rac1 and cofilin protein expression. To elucidate the role of NOS1AP in spine formation and synaptic function, we overexpressed NOS1AP isoforms in cultured rat cortical neurons. Overexpression of NOS1AP-L increases the number of immature spines, whereas overexpression of NOS1AP-S increases the number of mature and immature spines. In addition, overexpression of NOS1AP-S increases the frequency of miniature excitatory postsynaptic currents (mEPSCs) but not the amplitude. Overexpression of NOS1AP-L decreases the amplitude of mEPSCs but not the frequency. To investigate whether NOS1AP-L can mediate changes to dendrite patterning in vivo, we overexpressed NOS1AP-L in neuronal progenitor cells of the embryonic rat neocortex and analyzed dendrite patterning three weeks later. Neurons overexpressing NOS1AP-L in layers II/III of the neocortex exhibit a reduction in dendrite length and number. Finally, to investigate the role that NOS1AP plays in human dendritic arbor development, human neurons were generated using induced pluripotent stem cell technology. Overexpression of either NOS1AP-L or NOS1AP-S in human neurons results in a decrease in dendrite branching. Interestingly, treatment of human neurons with D-serine results in a reduction in NOS1AP-L protein expression. Taken together, our data support a role for NOS1AP-L and NOS1AP-S in dendritogenesis and synaptic function.
Subject
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Topic
Cell and Developmental Biology
RelatedItem
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TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier
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Identifier
ETD_6779
PhysicalDescription
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electronic resource
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application/pdf
InternetMediaType
text/xml
Extent
1 online resource (viii, 146 p. : ill.)
Note
(type = degree)
Ph.D.
Note
(type = bibliography)
Includes bibliographical references
Subject
(authority = ETD-LCSH)
Topic
Schizophrenia
Subject
(authority = ETD-LCSH)
Topic
Dendrites
Note
(type = statement of responsibility)
by Kristina Hernandez
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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NjNbRU
Identifier
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doi:10.7282/T3G44S8F
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
Hernandez
GivenName
Kristina
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime
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(point = start)
2015-09-24 19:27:48
AssociatedEntity
Name
Kristina Hernandez
Role
Copyright holder
Affiliation
Rutgers University. Graduate School - New Brunswick
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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.
RightsEvent
DateTime
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(point = start)
2015-10-31
DateTime
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2017-10-30
Type
Embargo
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after October 30th, 2017.
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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