{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/18643"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/18643","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"FMRP dependent synaptic delivery of messenger RNA","abstract":"Fragile X mental retardation is the most common inherited form of mental retardation. The loss of FMRP function results in Fragile X Mental Retardation. In this dissertation, I investigated the regulatory role of FMRP involved in synaptic mRNA delivery. In chapter 1, the molecular mechanism of local protein synthesis and synaptic mRNA delivery and its roles in Fragile X syndrome and learning and memory are introduced. In chapter 2, my data demonstrated that FMRP can facilitate mRNA deceleration and localization in dendritic spines upon neurotransmitter stimulation. Consistent with these findings, local protein synthesis was also enhanced in dendritic spines after stimulation. These results suggested that FMRP could mediate synaptic mRNA delivery for local protein synthesis. In Chapter 3, the role of FMRP splicing isoforms in synaptic mRNA delivery was investigated. My data suggested phosphorylation regulation and multiple isoforms of FMRP will be required to restore mRNA targeting to dendritic spines. In conclusion, synaptic mRNA delivery regulated by FMRP isoforms was demonstrated as a novel mechanism underlying altered cognitive deficits associated with Fragile X Syndrome. When mRNA cannot be targeted properly for translation, it may result in deficits in spine structure and neurological phenotypes, such as Fragile X Syndrome. My research also corroborates the importance of spatial accuracy of protein synthesis at a microscopic level in the nervous system.","abstract_html":"Fragile X mental retardation is the most common inherited form of mental retardation. The loss of FMRP function results in Fragile X Mental Retardation. In this dissertation, I investigated the regulatory role of FMRP involved in synaptic mRNA delivery. In chapter 1, the molecular mechanism of local protein synthesis and synaptic mRNA delivery and its roles in Fragile X syndrome and learning and memory are introduced. In chapter 2, my data demonstrated that FMRP can facilitate mRNA deceleration and localization in dendritic spines upon neurotransmitter stimulation. Consistent with these findings, local protein synthesis was also enhanced in dendritic spines after stimulation. These results suggested that FMRP could mediate synaptic mRNA delivery for local protein synthesis. In Chapter 3, the role of FMRP splicing isoforms in synaptic mRNA delivery was investigated. My data suggested phosphorylation regulation and multiple isoforms of FMRP will be required to restore mRNA targeting to dendritic spines. In conclusion, synaptic mRNA delivery regulated by FMRP isoforms was demonstrated as a novel mechanism underlying altered cognitive deficits associated with Fragile X Syndrome. When mRNA cannot be targeted properly for translation, it may result in deficits in spine structure and neurological phenotypes, such as Fragile X Syndrome. My research also corroborates the importance of spatial accuracy of protein synthesis at a microscopic level in the nervous system.","abstract_has_math":false,"creators":["Kao, Der-I"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Cell and Developmental Biology","degree_department":null,"school":null,"contributors":["Cox, Charles L.","Greenough, William T.","Chen, Jie"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2011,"date_issued":"2011-01-21T22:52:55Z","date_published":"2011-01-21T22:52:55Z","updated_at":"2026-07-22T22:25:11Z","subjects":["Fragile X Syndrome","Fragile X Mental Retardation Protein (FMRP)","mRNA targeting"],"languages":["en"],"rights":["Copyright 2010 Der-I Kao"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2142/18643","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Cox, Charles L.","Greenough, William T.","Chen, Jie"]},{"key":"dc:creator","label":"Author","values":["Kao, Der-I"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2011-01-21T22:52:55Z","2013-01-22T11:00:18Z","2010-12"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Cell and Developmental Biology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Fragile X Syndrome","Fragile X Mental Retardation Protein (FMRP)","mRNA targeting"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2010 Der-I Kao"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/18643"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Fragile X mental retardation is the most common inherited form of mental retardation. The loss of FMRP function results in Fragile X Mental Retardation. In this dissertation, I investigated the regulatory role of FMRP involved in synaptic mRNA delivery. In chapter 1, the molecular mechanism of local protein synthesis and synaptic mRNA delivery and its roles in Fragile X syndrome and learning and memory are introduced. In chapter 2, my data demonstrated that FMRP can facilitate mRNA deceleration and localization in dendritic spines upon neurotransmitter stimulation. Consistent with these findings, local protein synthesis was also enhanced in dendritic spines after stimulation. These results suggested that FMRP could mediate synaptic mRNA delivery for local protein synthesis. In Chapter 3, the role of FMRP splicing isoforms in synaptic mRNA delivery was investigated. My data suggested phosphorylation regulation and multiple isoforms of FMRP will be required to restore mRNA targeting to dendritic spines. In conclusion, synaptic mRNA delivery regulated by FMRP isoforms was demonstrated as a novel mechanism underlying altered cognitive deficits associated with Fragile X Syndrome. When mRNA cannot be targeted properly for translation, it may result in deficits in spine structure and neurological phenotypes, such as Fragile X Syndrome. My research also corroborates the importance of spatial accuracy of protein synthesis at a microscopic level in the nervous system.","Item withdrawn by Alexis Thompson (athmpsn1@illinois.edu) on 2010-11-24T19:15:47Z Item was in collections: University of Illinois Theses & Dissertations (ID: 1) No. of bitstreams: 1 Kao_Der-I.pdf: 2565530 bytes, checksum: 02d30758b8eee19bbf316886adbe0814 (MD5)","Made available in DSpace on 2011-01-21T22:52:55Z (GMT). No. of bitstreams: 2 Kao_Der-I.pdf: 2564131 bytes, checksum: 1f33fd02c4a3d3b6a4b96930296368bc (MD5) license.txt: 4057 bytes, checksum: 4dd7f1d43cf52a8da034be6cec08b2c6 (MD5)","Item marked as restricted to the 'Administrator' Group (id=1) by William Ingram (wingram2@illinois.edu) on 2011-01-21T22:54:05Z Item is restricted until 2013-01-21T22:53:34Z","Item reinstated by Sarah Shreeves (sshreeve@illinois.edu) on 2013-01-22T11:00:18Z Item was in collections: University of Illinois Dissertations and Theses (ID: 204) Dissertations and Theses - Cell and Developmental Biology (ID: 702) No. of bitstreams: 3 Kao_Der-I.pdf.txt: 136836 bytes, checksum: 7c18305274dcb6418ad1a8ded6f46657 (MD5) Kao_Der-I.pdf: 2564131 bytes, checksum: 1f33fd02c4a3d3b6a4b96930296368bc (MD5) license.txt: 4057 bytes, checksum: 4dd7f1d43cf52a8da034be6cec08b2c6 (MD5)","Item released from any restrictions by Sarah Shreeves (sshreeve@illinois.edu) on 2013-01-22T11:00:18Z"]},{"key":"dc:title","label":"Title","values":["FMRP dependent synaptic delivery of messenger RNA"]}]}],"canonical_facts":{"dc:contributor":["Cox, Charles L.","Greenough, William T.","Chen, Jie"],"dc:creator":["Kao, Der-I"],"dc:date":["2011-01-21T22:52:55Z","2013-01-22T11:00:18Z","2010-12"],"dc:description":["Fragile X mental retardation is the most common inherited form of mental retardation. The loss of FMRP function results in Fragile X Mental Retardation. In this dissertation, I investigated the regulatory role of FMRP involved in synaptic mRNA delivery. In chapter 1, the molecular mechanism of local protein synthesis and synaptic mRNA delivery and its roles in Fragile X syndrome and learning and memory are introduced. In chapter 2, my data demonstrated that FMRP can facilitate mRNA deceleration and localization in dendritic spines upon neurotransmitter stimulation. Consistent with these findings, local protein synthesis was also enhanced in dendritic spines after stimulation. These results suggested that FMRP could mediate synaptic mRNA delivery for local protein synthesis. In Chapter 3, the role of FMRP splicing isoforms in synaptic mRNA delivery was investigated. My data suggested phosphorylation regulation and multiple isoforms of FMRP will be required to restore mRNA targeting to dendritic spines. In conclusion, synaptic mRNA delivery regulated by FMRP isoforms was demonstrated as a novel mechanism underlying altered cognitive deficits associated with Fragile X Syndrome. When mRNA cannot be targeted properly for translation, it may result in deficits in spine structure and neurological phenotypes, such as Fragile X Syndrome. My research also corroborates the importance of spatial accuracy of protein synthesis at a microscopic level in the nervous system.","Item withdrawn by Alexis Thompson (athmpsn1@illinois.edu) on 2010-11-24T19:15:47Z Item was in collections: University of Illinois Theses & Dissertations (ID: 1) No. of bitstreams: 1 Kao_Der-I.pdf: 2565530 bytes, checksum: 02d30758b8eee19bbf316886adbe0814 (MD5)","Made available in DSpace on 2011-01-21T22:52:55Z (GMT). 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