The phenomenon of dendritic protein synthesis in neurons has been well documented. The specific mRNAs for several proteins with specific dendritic functions or localizations are thought to be targeted to sites of active translation in dendrites. This protein synthesis is associated with the postsynaptic side of synaptic contacts and may provide a mechanism for modulation of postsynaptic functional plasticity. However, the mechanisms for specific transport and targeting of RNA, to dendrites have not been delineated. This application will examine the specific structural elements responsible for localization of BC1, a short, neuron- specific RNA, to dendrites. The specific sequence elements required for targeting to dendrites will be determined and their ability to target foreign chimeric RNA sequences to the dendrite will be evaluated. In the second series of experiments, the role of electrical activity and synaptic transmission on the expression and transport of RNA into dendrites will be assessed. The effects of inhibitors for synaptic transmission, electrical activity, and cytoskeletal organization on various components of the translational apparatus will be examined. It is hoped that these studies will provide new insights into the role of dendritic protein synthesis in neuronal plasticity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS034158-01
Application #
2273294
Study Section
Neurology B Subcommittee 2 (NEUB)
Project Start
1994-08-01
Project End
1997-07-31
Budget Start
1994-08-01
Budget End
1995-07-31
Support Year
1
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Suny Downstate Medical Center
Department
Pharmacology
Type
Schools of Medicine
DUNS #
068552207
City
Brooklyn
State
NY
Country
United States
Zip Code
11203
Nimmrich, Volker; Hargreaves, Eric L; Muslimov, Ilham A et al. (2005) Dendritic BC1 RNA: modulation by kindling-induced afterdischarges. Brain Res Mol Brain Res 133:110-8
Kindler, Stefan; Wang, Huidong; Richter, Dietmar et al. (2005) RNA transport and local control of translation. Annu Rev Cell Dev Biol 21:223-45
Wang, Huidong; Tiedge, Henri (2004) Translational control at the synapse. Neuroscientist 10:456-66
Cristofanilli, Massimiliano; Thanos, Solon; Brosius, Jurgen et al. (2004) Neuronal MAP2 mRNA: species-dependent differential dendritic targeting competence. J Mol Biol 341:927-34
Muslimov, Ilham Aliagaevich; Nimmrich, Volker; Hernandez, Alejandro Ivan et al. (2004) Dendritic transport and localization of protein kinase Mzeta mRNA: implications for molecular memory consolidation. J Biol Chem 279:52613-22
Brosius, Jurgen; Tiedge, Henri (2004) RNomenclature. RNA Biol 1:81-3
Iacoangeli, Anna; Lin, Yuan; Morley, Eric J et al. (2004) BC200 RNA in invasive and preinvasive breast cancer. Carcinogenesis 25:2125-33
Muslimov, Ilham A; Titmus, Margaret; Koenig, Edward et al. (2002) Transport of Neuronal BC1 RNA in Mauthner Axons. J Neurosci 22:4293-301
Lein, Pamela J; Beck, Hiroko Nagasawa; Chandrasekaran, Vidya et al. (2002) Glia induce dendritic growth in cultured sympathetic neurons by modulating the balance between bone morphogenetic proteins (BMPs) and BMP antagonists. J Neurosci 22:10377-87
Wang, Huidong; Iacoangeli, Anna; Popp, Susanna et al. (2002) Dendritic BC1 RNA: functional role in regulation of translation initiation. J Neurosci 22:10232-41

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