Roles of carboxypeptidase E (CPE) in regulation of the microtubule cytoskeleton, neuronal migration, and dendrite morphology
Citation & Export
Hide
Simple citation
Liang, Chen.
Roles of carboxypeptidase E (CPE) in regulation of the microtubule cytoskeleton, neuronal migration, and dendrite morphology. Retrieved from
https://doi.org/doi:10.7282/T3GM8BFNExport
Description
TitleRoles of carboxypeptidase E (CPE) in regulation of the microtubule cytoskeleton, neuronal migration, and dendrite morphology
Date Created2017
Other Date2017-10 (degree)
Extent1 online resource (ix, 132 p. : ill.)
DescriptionCarboxypeptidase E (CPE) is a member of the M14 metallocarboxypeptidases family and is responsible for the proteolytic processing of peptide intermediates in endocrine cells and neurons. The importance of CPE in the nervous system has been elucidated in recent years. CPE-/- mice display a variety of neuronal deficits, including abnormal dendritic structure, spine morphology, and degeneration and deficits in learning and memory. It remains unclear whether and how CPE may contribute to neurodevelopment in addition to its role in prohormone processing, sorting, and transport. In this dissertation, I show that the level of CPE expression in mouse brain increases during embryonic and early postnatal development, and I demonstrate that it is enriched in and expressed throughout neurons. By overexpressing or knocking down CPE in vivo using the in utero electroporation technique, I find that CPE is required for proper cortical neuron migration. In hippocampal neuronal cultures, both overexpression and knockdown of CPE result in decreased dendrite branching, indicating that a balance of CPE protein level is required for proper dendrite morphogenesis. Importantly, I report that the interaction between the CPE carboxyl terminus and p150Glued is critical for regulation of the subcellular localization of p150(Glued), which may in turn affect the stability and dynamics of microtubule networks and may be responsible for the effects seen from CPE overexpression on dendrite morphology and neuronal migration. In addition, I identify a novel function for CPE in regulating tubulin polyglutamylation and show that the zinc-binding motif of CPE is required to mediate this activity. The role of CPE-mediated tubulin polyglutamylation in neuronal migration and dendrite branching is also examined, and my results show that this activity is not involved in regulation of these processes. Together, this study shows that CPE and its interactor, p150(Glued), are important players in neurodevelopment. Moreover, the zinc-binding motif of CPE and its function in regulating tubulin polyglutamylation play distinctive roles than does the CPE carboxyl terminus during early brain development.
NotePh.D.
NoteIncludes bibliographical references
Noteby Chen Liang
Genretheses, ETD doctoral
Languageeng
CollectionSchool of Graduate Studies Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
Statistical Profile