TitleThe roles of cypin in brain-derived neurotrophic factor (BDNF)-promoted neuronal dendrite branching and in the regulation of postsynaptic density-95 (PSD-95) protein levels
NameKwon, Munjin (author), Firestein, Bonnie L (chair), D'Arcangelo, Gabriella (internal member), Millonig, James H (internal member), Dreyfus, Cheryl F (outside member), Rutgers University, Graduate School - New Brunswick,
SubjectCell and Developmental Biology,
DescriptionAlterations in dendrite branching and morphology are present in many neurodegenerative diseases. These variations disrupt postsynaptic transmission and affect neuronal communication. Thus, it is important to understand the molecular mechanisms that regulate dendritogenesis and how they go awry during disease states. Previously, our laboratory showed that cypin, a guanine deaminase, increases dendrite number by regulating microtubule assembly. Cypin interacts with postsynaptic density-95 (PSD-95) protein, and reduces its synaptic clustering in cultured neurons when overexpressed. Brain-derived neurotrophic factor (BDNF) is one of most studied neurotrophins, which play a role in regulating neurite growth and branching in neurons. Here we examined the complex actions of cypin in BDNF-promoted dendrite branching and in regulating PSD-95 protein levels. First, we show the expression patterns of cypin and its new isoform in the developing rat brain. Second, we report that treatment of neurons with BDNF results in different effects, depending on how it is administered. Global administration of BDNF increases cypin mRNA and protein levels to regulate dendrite number only in the region proximal to the cell body. BDNF increases cypin levels via cyclic adenosine 3’5’-monophosphate (cAMP) response element-binding protein (CREB)-dependent transcriptional regulation by mitogen-activated protein kinase (MAPK) signaling pathways. Furthermore, localized BDNF application to the dendritic arbor also increases dendrite branching at sites of stimulation. Interestingly, local administration of BDNF increases dendrite branching not only proximal to the soma but also at distal regions in the arbor. Taken together, these studies suggest that distinct sources of BDNF regulate dendritic arborization via different mechanisms. Finally, we investigate the role of cypin on the expression of its binding partner, PSD-95. Overexpression of cypin increases total cellular PSD-95 levels, and this effect is occluded by treatment with a proteasome inhibitor. Since PSD-95 is important for assembling signaling complexes and mediating synaptic activity, a role for cypin at synaptic sites in proteasome-dependent regulation of PSD-95 is proposed. Therefore, we suggest new roles of cypin in BDNF-promoted dendrite branching and in the alteration of PSD-95 protein levels at synaptic sites.
NoteIncludes bibliographical references
Noteby Munjin Kwon
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.