Neuronal maturation, function and plasticity depend on
a large number of intricate cellular processes, which allow
individual neurons to function within a larger network.
Our current focus is on two of the cellular processes crucial
to the neuron: axonal transport and regulated RNA splicing.
We use the fruit fly Drosophila because of the superior
genetic and transgenic technologies it offers.
Transport along the cytoskeleton is the primary mechanism
by which materials are distributed to the various subcellular
compartments within the highly polarized neuronal cell.
Delivery of materials to the axonal and dendritic terminals
and transmission of signals back from the terminals to the
cell body are important to growth and function of neurons.
We have shown in Drosophila, that APPL protein (homologous
to the human ß amyloid protein precursor associated with
Alzheimer's disease) affects axonal transport. Starting
with a background that compromises axonal transport we are
identifying other genes/proteins that are involved in this
process.
We have also demonstrated that APPL has a synapse promoting
activity that could be important in neuronal plasticity.
Long term goals of this research are to elucidate APPL receptor
induced signal transduction mechanisms and understand the
relation between APPL function and Alzheimer disease condition.
Another area of our research addresses the role of ELAV,
a neuron-specific post-transcriptional regulator in neuronal
development. We have demonstrated that ELAV, a RNA binding
protein regulates neural specific splicing of transcripts
of three genes: neuroglian, erect wing and armadillo. Current studies are aimed at finding the
cohort of genes regulated by ELAV, the developmental role
of ELAV-regulated splicing and mechanism of ELAV-regulation.
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Selected Publications:
Soller M and White, K. (2004) ELAV. Current Biology 14: R53.
Soller M, White K. (2003) ELAV inhibits 3'-end processing
to promote neural splicing of ewg pre-mRNA. Genes Dev. 17:2526-38. [abstract]
Toba G, Qui J, Koushika SP, White K. (2002) Ectopic expression
of Drosophila ELAV and human HuD in Drosophila wing disc
cells reveals functional distinctions and similarities. J Cell Sci. 115(Pt 11):2413-21. [abstract]
Lisbin MJ, Qiu J, White K. (2001) The neuron-specific RNA-binding
protein ELAV regulates neuroglian alternative splicing in
neurons and binds directly to its pre-mRNA. Genes Dev. 15:2546-61. [abstract]
Torroja, L., Packard, M., Budnik, V and K. White K. (2000).
Overexpression of APPL, a Drosophila APP homologue, compromises
microtubule associated axonal transport and promotes synapse
formation. In Neurodegenerative diseases: gain of function
through loss of function. Eds: Master, Beyreuther and Christen,
Publisher- Springer-Verlag.
Lisbin, M. J., Gordon, M., Yannoni, Y. M. and K. White
(2000). Function of RRM domains of Drosophila ELAV:
RNP1 Mutations and RRM Domain Replacements with ELAV Family
Proteins and SXL. Genetics 155: 1789-1798.
[abstract]
Lisbin, M. J., Gordon, M., Yannoni, Y. M. and K. White
(2000). Function of RRM domains of Drosophila ELAV:
RNP1 Mutations and RRM Domain Replacements with ELAV Family
Proteins and SXL. Genetics 155: 1789-1798.
[abstract]
Koushika, S.P., Soller, M., and K. White (2000) Neuron-enriched
splicing pattern of Drosophila erect wing is dependent on
the presence of ELAV protein. Mol. Cell. Bio. 20:1836-1845.
[abstract]
Yannoni, Y. M., and K. White (1999). Domain necessary for
Drosophila ELAV nuclear localization: Function requires
nuclear ELAV. J. Cell Science. J. Cell Sci. 112: 4501-4512.
[abstract]
Torroja, L., Packard, M., Gorczyca, M., White K., and V.
Budnik (1999) The Drosophila ß-Amyloid Precursor
Protein Homolog Promotes Synapse Differentiation at the
Neuromuscular Junction. J. Neuroscience 19: 7793-7803. [abstract]
Torroja, L., Chu, H., Kotovsky, I., and K. White (1999)
Neuronal ovrexpression of APPL, the Drosophila homologue
of amyloid precursor protein (APP), disrupts axonal transport.
Current Biology. 9: 489-422. [abstract]
Koushika, S.P., Soller, M., DeSimone, S. M. Daub, D.M.,
and K. White (1999) Differential and inefficient splicing
of a broadly expressed Drosophila erect wing transcript
results in tissue-specific enrichment of the vital EWG protein
isoform. Mol. Cell. Bio. 19: 3998-4007. [abstract]
Chu, H., Parras, C., White, K., and F. Jimenez (1998) Formation
and specification of ventral neuroblasts is controlled by
vnd in Drosophila neurogenesis. Genes Dev. 12:3613-3624.
[abstract]
Yannoni, Y. M., and K. White (1997) Association of the
neuron-specific RNA binding domain containing protein ELAV
with the coiled body in Drosophila neurons. Chromosoma 105:
332-341. [abstract]
Koushika, S.P., Lisbin, J.M., and K. White (1996) ELAV,
a Drosophila neuron-specific protein mediates the generation
of an alternatively spliced neural protein isoform. Current
Biology 6: 1634-1642. [abstract]
Torraja, L., Luo, L., and K. White (1996) APPL, the Drosophila
member of the APP-family, exhibits differential trafficking
and processing in CNS neurons J. Neuroscience 16: 4638-50.
[abstract]
View Complete Publication List on PubMed: Kalpana White
Last reviewed: Nov. 7, 2005