Areas of Interest
Neural cell biology, mRNA trafficking and myelin and synapse
formation.
Our laboratory studies the mechanism and regulation of mRNA
transport, localization, and translation in oligodendrocytes and
neurons. An 11-nucleotide sequence first identified in the 3’UTR
of myelin basic protein, a major and essential component of
myelin, is also present in several neuronal mRNAs (CamKII,
neurogranin, arc, etc.) implicated in synaptic plasticity. This
sequence is recognized by the protein hnRNP A2 which in turn
binds to TOG (tumor overexpressed gene) protein. The function of
TOG may be to assemble mRNAs whose proteins function in an
interdependent manner, in the same complex or RNA granule so
that they can be regulated coordinately.
Lab Rotation Projects
Characterization of a conditional TOG knockout mouse.
TOG is found in granules that transport mRNAs such as CamKII,
neurogranin, arc, FMRP (fragile mental retardation protein) in
dendrites for translation at or near synapses. We have generated
a conditional TOG knockout mouse using the cre-lox systen. We
have begun the characterization of mice in which TOG was
specifically abolished in neurons of the hippocampus.
Preliminary data indicate that these mice have learning deficits
and are hyperactive and suggest that dysregulation of
translation may be responsible for these symptoms. Further
analysis needs be carried out at the behavioral, cellular and
molecular levels in order to identify the role and mode of
action of TOG in neurons, and to determine if the knockout mouse
can be a model for autism.
Regulation of translation of messages that are translated
at sites distant from the cell body.
Messenger RNAs that are synthesized in the myelin of
oligodendrocytes or in the dendrites of neurons are kept silent
during their transport from the cell body to their final
destination. We aim to identify the components involved in
silencing mRNAs during their transport. The project will involve
analyzing how components of the transport machinery and those of
the translation machinery interact with each other to regulate
translation. Protein-protein interactions will be studied in
vitro, in cell extracts, and in live cells using fluorescently
tagged molecules. Transport and translation assays are done in
cultured oligodendrocytes and/or neurons under a variety of
conditions. Understanding the mechanism that silence translation
in oligodendrocytes may have relevance to multiple sclerosis.
Laboratory
Page
Selected Publications
Carson JH, Gao Y, Tatavarty V, Levin MK, Korza G, Francone VP,
Kosturko LD, Maggipinto MJ, Barbarese E. (2008). Multiplexed RNA
trafficking in oligodendrocytes and neurons. Biochim Biophys
Acta. 1779:453-8
Francone, V.P., Maggipinto, M.J., Kosturko, L.D., and
Barbarese, E. (2007). The microtubule-associated protein tumor
overexpressed gene/cytoskeleton-associated protein 5 is
necessary for myelin basic protein expression in
oligodendrocytes. J. Neurosci. 27:7654-7652.
Kosturko LD, Maggipinto MJ, Korza G, Lee JW, Carson JH,
Barbarese E.
Heterogeneous nuclear ribonucleoprotein (hnRNP) E1 binds to
hnRNP A2 and inhibits translation of A2 response element mRNAs.
Mol Biol Cell. 2006 Aug;17(8):3521-33.
Kosturko LD, Maggipinto MJ, D'Sa C, Carson JH, Barbarese E.
The microtubule-associated protein tumor overexpressed gene
binds to the RNA trafficking protein heterogeneous nuclear
ribonucleoprotein A2. Mol Biol Cell. 2005 Apr;16(4):1938-47.
Maggipinto, A., Rabiner, C., Kidd, G.J., Hawkins, A.J.,
Smith, R., and Barbarese, E. Increased expression of the MBP
mRNA binding protein hnRNP A2 during oligodendrocyte
differentiation. J. Neurosci. Res. 75:614-623 (2004).
Shan, J, Munro T.P., Barbarese, E., Carson, J.H., and Smith,
R. A molecular mechanism for mRNA transport in neuronal
dendrites. J. Neurosci.23:8859-8866 (2003).
Song, J., Carson, J.H., Barbarese, E., Li, F.Y., and Duncan,
I.D. Anterograde RNA transport is inhibited in microtubule
defective oligodendrocytes. Mol. Cell Neurosci. 24:926-938
(2003).
Huang, Y.S., Carson, J.H., Cao, Q., Barbarese, E., and
Richter, J.D. Facilitation of dendritic mRNA transport by CPEB.
Genes & Development 17:638-653 (2003).
 View more publications, see
Pubmed listing.
rev. 3/09 |
