Abstract

Neural cells exhibit highly polarized morphology and functions which undergo plastic changes in response to external stimuli. This is the basis for neurogenesis, gliogenesis, synaptogenesis, myelin morphogenesis, gliosis, synaptic plasticity and learning and memory. Intracellular trafficking and localized translation of specific mRNAs play a key role in establishing and maintaining morphological and functional polarity and in mediating plasticity. This is a proposal to investigate the molecular mechanisms of intracellular trafficking and localized translation of myelin basic protein (MBP) mRNA in oligodendrocytes. MBP mRNA follows a defined multistep intracellular trafficking pathway from the nucleus through the perikaryon and processes to the myelin compartment. One particular cis-acting sequence in the 3'UTR of MBP mRNA, termed the RNA transport/transplantation sequence (RTS), is involved in several steps of this pathway. Several other transported RNAs also contain RTS-like sequences. The RTS binds to the trans-acting factor, hnRNPA2 (A2). The overall goal of the proposal is to elucidate how TRS/A2 determinants are involved in intracellular RNA trafficking in oligodendrocytes. The results will provide a paradigm for understanding intracellular RNA trafficking in neural cells in general. This will be important for elucidating the molecular mechanisms mediating polarity and plasticity in the nervous system.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS015190-21
Application #
6126086
Study Section
Neurology C Study Section (NEUC)
Program Officer
Behar, Toby
Project Start
1979-04-01
Project End
2001-11-30
Budget Start
1999-12-01
Budget End
2000-11-30
Support Year
21
Fiscal Year
2000
Total Cost
$229,260
Indirect Cost

  Institution

Name
University of Connecticut
Department
Biochemistry
Type
Schools of Medicine
DUNS #
City
Farmington
State
CT
Country
United States
Zip Code
06030

  Publications

Falkenberg, Cibele Vieira; Carson, John H; Blinov, Michael L (2017) Multivalent Molecules as Modulators of RNA Granule Size and Composition. Biophys J 113:235-245
Giampetruzzi, Anthony; Carson, John H; Barbarese, Elisa (2013) FMRP and myelin protein expression in oligodendrocytes. Mol Cell Neurosci 56:333-41
Tatavarty, Vedakumar; Ifrim, Marius F; Levin, Mikhail et al. (2012) Single-molecule imaging of translational output from individual RNA granules in neurons. Mol Biol Cell 23:918-29
Chen, Yan; Bai, Ping; Mackay, Shannon et al. (2011) Herpes simplex virus type 1 helicase-primase: DNA binding and consequent protein oligomerization and primase activation. J Virol 85:968-78
Francone, Victor P; Ifrim, Marius F; Rajagopal, Chitra et al. (2010) Signaling from the secretory granule to the nucleus: Uhmk1 and PAM. Mol Endocrinol 24:1543-58
Han, Siew Ping; Friend, Lexie R; Carson, John H et al. (2010) Differential subcellular distributions and trafficking functions of hnRNP A2/B1 spliceoforms. Traffic 11:886-98
Levin, Mikhail K; Hingorani, Manju M; Holmes, Raquell M et al. (2009) Model-based global analysis of heterogeneous experimental data using gfit. Methods Mol Biol 500:335-59
Eisenberg, Shlomo; Korza, George; Carson, John et al. (2009) Novel DNA binding properties of the Mcm10 protein from Saccharomyces cerevisiae. J Biol Chem 284:25412-20
Paradise, Allison; Levin, Mikhail K; Korza, George et al. (2007) Significant proportions of nuclear transport proteins with reduced intracellular mobilities resolved by fluorescence correlation spectroscopy. J Mol Biol 365:50-65
Kosturko, Linda D; Maggipinto, Michael J; Korza, George et al. (2006) Heterogeneous nuclear ribonucleoprotein (hnRNP) E1 binds to hnRNP A2 and inhibits translation of A2 response element mRNAs. Mol Biol Cell 17:3521-33

Showing the most recent 10 out of 28 publications