In 1989, Dr. Krämer completed his Ph.D. at the University of Cologne, Germany, where he worked on DNA looping in the lac operon. As a postdoctoral fellow in the lab of Dr. Larry Zipursky at UCLA, he studied cell-cell interactions during neuronal differentiation in the compound eye of Drosophila. In 1993, he joined UT Southwestern as an Assistant Professor in Cell Biology and Neuroscience.
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.
Lloyd, V., Ramaswami, M. and Krämer, H. (1998) Not just pretty eyes: Drosophila eye color mutations and lysosomal delivery. Trends in Cell Biology 8, 257-259.
Sunio, A., Metcalf, A. and Krämer, H. (1999). 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.
Sevrioukov, E., He, J.-P., Sunio, A, Moghrabi N. and Krämer H. (1999). A role for the deep orange and carnation eye-color genes in lysosomal delivery in Drosophila. Molecular Cell 4, 479-486.
Narayanan, R., Krämer, H. and Ramaswami, M. (2000) Drosophila endosomal proteins Deep Orange and Hook regulate synapse size but not synaptic vesicle recycling. J. of Neurobiology 45,105-119.
Walenta, J., Didier, A., Liu, X. and Krämer, H. (2001). The Golgi-Associated Hook3 Protein is a Member of a Novel Family of Microtubule-Binding Proteins. J. Cell Biol. 152, 923-934.
Shotland, Y, Krämer H., and Eduardo A. Groisman (2003) The Salmonella SpiC protein targets the mammalian Hook3 protein to alter cellular trafficking. Mol. Microbiology 49, 1565-1576.
Sevrioukov, E., Moghrabi N. Kuhn, M. and Krämer H. (2005) A mutation in dVps28 reveals a link between ESCRT-I complex function and the actin cytoskeleton in Drosophila. Mol. Biol. Cell 16, 2301-2312.
Pulipparacharuvil, S., Akbar, A. Ray, S., Sevrioukov, E.A., Haberman A.S. and Krämer H. (2005) Drosophila Vps16A is required for trafficking to lysosomes and pigment granule biogenesis J. Cell Science 15, 3663-73.
Szebenyi, G., Hall B., Yu, R., Hashim A. I, and Krämer, H. (2007) Hook2 localizes to the centrosome, binds directly to Centriolin/CEP110, and contributes to centrosomal function. Traffic 8, 32-46.
Sano, H., Ishino, M., Krämer, H., Shimizu, T., Mitsuzawa, H., Nishitani, C., and Kuroki, Y. (2007) The microtubule binding protein Hook3 interacts with a cytoplasmic domain of scavenger receptor. A. J. Biol. Chem 282, 7973-7981.
Szebenyi, G., Wigley, W.C., Hall B., Didier, A., Yu, M., Thomas, P., and Krämer, H. (2007) Hook2 contributes to aggresome formation. BMC Cell Biol. 8:19-28.
Krämer, H. and Kavalali, E.T. (2008) Dynamin-independent synaptic vesicle retrieval? Nat Neuroscience 11, 6-8.
Akbar, M.A., Ray, S., and Krämer, H. (2009) The SM Protein Car/Vps33A is Necessary for SNARE-Mediated Trafficking to Lysosomes and Lysosome-Related Organelles. Mol Biol. Cell 20, 1705-1714.