As the nervous system organizes itself its individual cells must communicate with each other. Much of this information exchange involves the activation of cell surface receptors, including Notch and EGF receptor. Such signals are regulated by multiple mechanisms one of which is the internalization and endocytic trafficking of receptors and ligands. Research in our lab focuses on the genetic and molecular dissection of endocytic trafficking. We use the Drosophila compound eye as a model system to identify and characterize a variety of proteins required for trafficking of cell surface proteins. Among them, we found Deep orange and Carnation proteins to be part of a complex necessary for the delivery of cargo to lysosomes and pigment granules. By contrast, dVps28 encodes one of the type I ESCRT proteins involved in the sorting of cargo into multivesicular late endosomes. Several other novel endocytic trafficking mutations are being currently explored. Interestingly, ESCRT proteins as well as Deep orange and Carnation are also required for the normal progression of autophagy. This process allows cells to deliver cytosolic content to lysosomes and has a well-established role in cellular responses to starvation. Autophagy also appears to be the last resort of neurons to combat harmful protein aggregates typical for many neurodegenerative diseases. We are therefore exploring the mechanisms by which some of the novel endocytic regulators that we identified are modulating autophagosome maturation.
RESEARCH INTERESTS
Research in Dr. Kramer's lab focuses on the genetic and molecular dissection of late endocytic trafficking. The lab uses the Drosophila compound eye as a model system to identify mutations altering membrane traffic from the cell surface to different organelles. One class of genes, exemplified by deep orange and carnation, is necessary for the delivery of cargo to lysosomes and pigment granules.
The hook gene represents a second class of mutations necessary for normal lysosomal delivery. Hook proteins are a novel family of microtubule-binding proteins that play a role in the positioning of different organelles. To investigate the molecular mechanisms by which these proteins effect membrane trafficking we are combining genetic and cell biological approaches in Drosophila and mammalian cells.
RECENT PUBLICATIONS
Kramer, H. and Kavalali, E.T., "Dynamin-independent synaptic vesicle retrieval?" Nature Neuroscience, 11:6-8, January 2008
Szebenyi,, G., Hall B., Yu, R., Hashim A. I, and Kramer, H., "Hook2 localizes to the centrosome, binds directly to Centriolin/CEP110, and contributes to centrosomal function." Traffic, 8:32-46, 2007
Szebenyi G, Wigley WC, Hall B, Didier A, Yu M, Thomas P, Kramer H., "Hook2 contributes to aggresome formation." BMC Cell Biol, 8:19-29, May 2007
Sevrioukov, E., Moghrabi, N., Kuhn, M., and Kramer, H., "A mutation in dVps28 reveals a link between the ESCRT-I complex and the actin cytoskeleton in Drosophila" Mol. Biol. Cell, 16:2301?2312, 2005
Pulipparacharuvil, S., Akbar, A. Ray, S., Sevrioukov, E.A., Haberman A.S. and Kramer H, "Drosophila Vps16A is required for trafficking to lysosomes and pigment granules biogenesis" J. Cell Science, 118:3663-3673, 2005
SIGNIFICANT PUBLICATIONS
Akbar, M.A., Ray, S., and Kramer, H., "The SM Protein Car/Vps33A is Necessary for SNARE-Mediated Trafficking to Lysosomes and Lysosome-Related Organelles" Mol Biol Cell, 20:1705-1714, March 2009
Walenta, J., Didier, A., Liu, X. and Kramer, H., "The Golgi-Associated Hook3 Protein is a Member of a Novel Family of Microtubule-Binding Proteins." J. Cell Biol., 152:923-934, March 2001
Sevrioukov, E., He, J.-P., Sunio, A, Moghrabi N. and Kramer H., "A role for the deep orange and carnation eye-color genes in lysosomal delivery in Drosophila" Molecular Cell, 4:479-486, November 1999
Sunio, A., Metcalf, A. and Kramer, H., "Genetic dissection of endocytic trafficking in Drosophila using a horseradish peroxidase-bride of sevenless chimera: hook is required for normal maturation of multivesicular endosomes" Mol. Biol. Cell, 10:847-859, April 1999
Kramer, H., Cagan, R.L. and Zipursky, S.L., "Interaction of bride of sevenless membrane-bound ligand and the sevenless tyrosine-kinase receptor." Nature, 352:207-212, May 1991
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