Kalpana White
Professor Emerita of Biology
Research Description
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 focus was on two of the cellular processes crucial to the neuron: axonal transport and regulated RNA splicing. We used 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 also demonstrated that APPL has a synapse promoting activity that could be important in neuronal plasticity. Long term goals of this research was to elucidate APPL receptor induced signal transduction mechanisms and understand the relation between APPL function and Alzheimer disease condition.
Another area of our research addressed the role of ELAV, a neuron-specific post-transcriptional regulator in neuronal development. We demonstrated that ELAV, a RNA binding protein regulates neural specific splicing of transcripts of three genes: neuroglian, erect wing and armadillo. Studies were aimed at finding the cohort of genes regulated by ELAV, the developmental role of ELAV-regulated splicing and mechanism of ELAV-regulation.
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-RNA. Genes Dev. 17:2526-38.
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.
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.
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.
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.
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.
Yannoni, Y. M., and K. White (1999). Domain necessary for Drosophila ELAV nuclear localization: Function requires nuclear ELAV. J. Cell Science 112: 4501-4512.
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.
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.
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.
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.
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.
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.
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.