Huaye Zhang
Univ Of Med/dent Nj-r W Johnson Med Sch
Project start date: 2009-05-01
Project end date: 2013-12-31
Sponsored Links Excellgen http://Excellgen.com
Grants awarded to Huaye Zhang
THE PAR-6/APKC POLARITY COMPLEX IN SYNAPTIC ASSEMBLY AND FUNCTION
Huaye Zhang
University Of Virginia Charlottesville, Box 400195, Charlottesville, Va 22904-4195
Grant 5K99NS065183-02 from National Institute Of Neurological Disorders And Stroke
Abstract: This proposal is based on the finding that the PAR-6/aPKC polarity complex regulates dendritic spine morphogenesis, and that it does so through a novel pathway involving p190 RhoGAP and the RhoA GTPase. My goal during the mentored phase of this proposal is to learn electrophysiological approaches required to address whether the PAR-6/aPKC complex regulates synaptic function, and to extend my studies to an in vivo environment by generating a conditional PAR-6 knockout mouse. I will also learn the. mouse behavioral approaches to incoporate into my future research. The mentored phase research will be carried out in the University of Virginia. I will be mentored by Dr. Ian Macara (primary mentor), Dr. Suzanne Moenter (co-mentor), Dr. Julius Zhu and Dr. Scott Zeitlin (mentoring committee members). For the independent phase, I will continue to explore the function of the PAR-6/aPKC complex in synaptic assembly and function, both in dissociated neuronal cultures and in vivo. The specific questions that I would like to address during this phase are What are the upstream regulators of the PAR-6/aPKC complex? What is the molecular basis for the activation of p190 RhoGAP by PAR-6/aPKC? Is PAR-6 involved in synaptic plasticity and memory formation in vivo? Together, these studies will provide significant insight into the role of the PAR-6/aPKC complex in regulating synaptic function. My long term goal is to understand the complex signaling mechanisms regulating synaptic assembly and function, and how they relate to memory formation in vivo. I will use a combination of cell biological, electrophysiological and behavioral approaches to address these questions. The goal of this research proposal is to understand the effects of a group of proteins called PAR-6 and aPKC on the way brain cells connect with each other. The results can have significant implications in various neurological disorders including mental retardation, schizophrenia and Alzheimer´s disease
Keywords: Actins; Address; Affect; Alzheimer; Alzheimer disease; Alzheimer sclerosis; Alzheimer syndrome; Alzheimer`s; Alzheimer`s Disease; Alzheimers Dementia; Alzheimers disease; Ammon Horn; Behavioral; Biochemical; Biological; Brain; C elegans; C.elegans; CASPR; CNTNAP; CNTNAP1; CNTNAP1 gene; Caenorhabditis elegans; Cell Communication and Signaling; Cell Signaling; Cell surface; Cells; Clinical; Committee Members; Complex; Contactin Associated Protein 1 Gene; Cornu Ammonis; Data; Degenerative Diseases, Nervous System; Degenerative Neurologic Disorders; Dementia, Alzheimer Type; Dementia, Primary Senile Degenerative; Dementia, Senile; Dendritic Spines; Electrophysiology; Electrophysiology (science); Encephalon; Encephalons; Environment; Excitatory Synapse; Future; GTP Phosphohydrolases; GTPases; Glutamate Receptor; Glutamates; Goals; Guanosine Triphosphate Phosphohydrolases; Guanosinetriphosphatases; Hippocampus; Hippocampus (Brain); Intracellular Communication and Signaling; JTB Protein; JTB protein, human; Jumping Translocation Breakpoint Protein; Knockout Mice; L-Glutamate; Learning; Maintenance; Maintenances; Mammals, Mice; Mass Spectrum; Mass Spectrum Analysis; Mediating; Members, Committee; Memory; Memory Deficit; Memory impairment; Mental Retardation; Mentors; Methods; Methods and Techniques; Methods, Other; Mice; Mice, Knock-out; Mice, Knockout; Molecular; Morphogenesis; Murine; Mus; NRXN4; Nerve Cells; Nerve Impulse Transmission; Nerve Transmission; Nerve Unit; Nervous System Diseases; Nervous System Physiology; Nervous System, Brain; Neural Cell; Neural Transmission; Neurexin 4 Gene; Neurexin IV Gene; Neurocyte; Neurodegenerative Diseases; Neurodegenerative Disorders; Neurologic Degenerative Conditions; Neurologic Diseases, Degenerative; Neurologic Disorders; Neurologic function; Neurological Disorders; Neurological function; Neuronal Transmission; Neurons; Neurophysiology / Electrophysiology; Null Mouse; P190; PAR Protein; PAR protein, human; PAR-6; PAR-6A; PAR6Alpha; PARD6A; PARD6A gene; Pathway interactions; Phase; Phosphorylation; Photometry/Spectrum Analysis, Mass; Primary Senile Degenerative Dementia; Process; Prostate Androgen Regulated Protein; Protein Phosphorylation; Proteins; Regulation; Research; Research Proposals; Role; Schizophrenia; Schizophrenic Disorders; Signal Transduction; Signal Transduction Systems; Signaling; Spectrometry, Mass; Spectroscopy, Mass; Spectrum Analyses, Mass; Spectrum Analysis, Mass; Spinal Column; Spine; Structure; Synapses; Synaptic; Synaptic Transmission; Synaptic plasticity; TAX40; TIP-40; Techniques; Testing; Translating; Translatings; Transmission; Universities; Vertebral column; Virginia; atypical protein kinase C; backbone; base; biological signal transduction; brain cell; cognitive function; dementia of the Alzheimer type; dementia praecox; dendrite spine; gene product; guanosinetriphosphatase; hippocampal; human JTB protein; in vivo; insight; language translation; nervous system disorder; nervous system function; neurodegenerative illness; neurological disease; neuronal; neurotransmission; novel; pathway; primary degenerative dementia; prostate androgen regulated protein, human; public health relevance; response; rho; rho GTPase-activating protein; rhoGAP; schizophrenic; senile dementia of the Alzheimer type; social role; synapse function; synaptic function; transmission process
Project start date: 2009-05-01
Project end date: 2011-04-30
Budget start date: 1-MAY-2010
Budget end date: 30-APR-2011
PFA/PA: PA-07-297
5K99NS065183-02 (2010): $89999