Patricia Scott

Contact Information Phone: 218-726-7049 Fax: 218-726-8014 Email: pscott@d.umn.edu Address: 269 SMed 1035 University Dr. Duluth, MN 55812

Research Assistant Professor

Research

GGA proteins facilitate accurate intracellular protein transport.

Many proteins are delivered to specific intracellular locations by membrane trafficking. In this process membrane-spanning proteins, also known as cargo proteins, are recruited into membrane-bound vesicles that bud off to ferry proteins to their correct destination. Accurate recruitment of membrane-spanning proteins, also known as cargo protein sorting, is a critical first step in delivery of these proteins to their correct final destination.

The GGA (Golgi-localized, Gamma-adaptin ear homology, ARF-binding) family of proteins facilitates cargo protein sorting. GGA proteins from yeast to humans share a conserved modular domain structure with each domain interacting with specific binding partners. It is thought that the multi-domain structure of GGAs allows them to act as adapters that promote formation of sorting complexes by binding simultaneously to cargo proteins and elements of the sorting machinery.

Recent work in our lab and others has established that GGA proteins bind directly to ubiquitin. This result is significant because covalent attachment of ubiquitin to membrane-spanning cargo proteins acts as a sorting signal throughout endosomal membrane trafficking pathways. Thus, interaction of GGAs with ubiquitin may allow GGAs to recognize and sort specific cargo proteins.

Our model is that GGAs promote sorting of specific cargo proteins into a specific membrane trafficking pathway, the endosomal pathway. Endosomal trafficking contributes to maintaining the correct balance of membrane spanning proteins at the cell surface and thus the correct balance of proliferatory and anti-proliferatory signals to the cell. To understand the changes that occur in malignant cells, and in other disease states we are identifying GGA-dependent cargo and GGA-associated sorting complexes. These proteins will potentially provide targets for diagnosis, prevention or treatment of human disease.

Education

Ph.D. University of Wisconsin, Madison, 1997

Laboratory Personnel

Katherine Backes, undergraduate Katie Bendickson, undergraduate Jacob Moe, undergraduate Allison Peterson, undergraduate

Publications

Publications on PubMed

Recent Publications
Scott, P., M.A. Kessler, and L.A. Schuler. Molecular cloning of the bovine prolactin receptor and distribution of prolactin and growth hormone receptor transcripts in fetal and uteroplacental tissues. Molecular and Cellular Endocrinology 89:47-58, 1992.

Schuler, L.A., P. Scott, and M.A. Kessler. "Molecular genetics and biology of the bovine placental prolactin family." In: Trophoblast Cells: Pathways for Maternal-Embryonic Communication . M.J. Soares, S. Handwerger, and F. Talamantes, eds. Springer-Verlag, New York, pp. 191-205, 1993.

Eisenbraun, T.L., P.M. Scott, G.D. Kennedy, and J.E. Niederhuber. (2001) "Mechanisms and regulation of eukaryotic protein synthesis." In: Surgical Research. W. Souba and D. Wilmore, ed. Academic Press, San Diego, CA, pp. 271-284.

Lu, J.-C., P. Scott, G.J. Strous, and L.A. Schuler. (2002) Multiple Internalization
Motifs Differentially Utilized by Prolactin Receptor Isoforms Mediate Similar Endocytic Pathways. Molecular Endocrinology 16(11), 2515-2527.

Scott, P., P. Bilodeau, O. Zhdankina, S. Winistorfer, M. Hauglund, M. Allaman, W. Kearney, A. Robertson, A. Boman, R. Piper. (2004) GGA proteins bind ubiquitin to facilitate cargo sorting at the trans-Golgi network in yeast. Nature Cell Biology 6, 252-259.

Abstracts
Zhdankin, O., E. Peterson, M. Broderius, J. Moe, M. Hauglund, P. Scott. (2005) GGA clathrin adapter proteins and ion homeostasis in yeast. Keystone Symposium, Ubiquitin and Signaling. Taos, NM.

Scott, P., M.J. Hauglund, O. Zhdankina, P.S. Bilodeau, R.C. Piper, and A.L. Boman. (2003) GGA proteins bind ubiquitin to facilitate cargo sorting at the trans-Golgi network in yeast. American Society for Cell Biology, 43rd Annual Meeting, San Francisco, CA, December 14.

Scott, P., E. Stevens, J.E. Niederhuber. (2001) Membrane sub-domain localization and Blk response to BCR stimulation. Wisconsin Symposium 11: Genes, Genomes and Molecules. Madison, WI.

Lu, J.-C., P. Scott, and L.A. Schuler. (2000) Role of ubiquitin and dynamin in prolactin receptor internalization. Minisymposium: Cell Signaling and Growth Control, University of Wisconsin Comprehensive Cancer Center and Promega Corporation.

Scott, P. and L.A. Schuler. (1997) PRLR long form is internalized more rapidly than the short form. 79th Annual Meeting of the Endocrine Society, Minneapolis, MN.

Scott, P. and J.E. Niederhuber. (1999) Comparison of localization of Src-like kinases Blk and Lyn to a membrane subdomain. Cold Spring Harbor Laboratory Symposium on Signaling and Gene Expression in the Immune System, p. 190.

Scott, P., R. Nagel, M.A. Kessler, and L.A. Schuler. (1996) Lactogenic hormones down-regulate prolactin receptor expression in a bovine endometrial cell line overexpressing the prolactin receptor. 10th International Congress of Endocrinology, San Francisco, CA, P1-704, 1996.

Scott, P. and L.A. Schuler. (1994) Characterization of two bovine endometrial cell lines. 76th Annual Meeting of the Endocrine Society, Anaheim, CA, Abs. 1405.

Scott, P., P. Bilodeau, O. Zhdankina, S. Winistorfer, M. Hauglund, M. Allaman, W. Kearney, A. Robertson, A. Boman, R. Piper. (2004) GGA proteins bind ubiquitin to facilitate cargo sorting at the trans-Golgi network in yeast. Nature Cell Biology 6, 252-259.

Lu, J.-C., P. Scott, G.J. Strous, and L.A. Schuler. (2002) Multiple Internalization
Motifs Differentially Utilized by Prolactin Receptor Isoforms Mediate Similar Endocytic Pathways. Molecular Endocrinology 16(11), 2515-2527.

Eisenbraun, T.L., P.M. Scott, G.D. Kennedy, and J.E. Niederhuber. (2001) Mechanisms and regulation of eukaryotic protein synthesis. In: Surgical Research. W. Souba and D. Wilmore, ed. Academic Press, San Diego, CA, pp. 271-284.

Schuler, L.A., P. Scott, and M.A. Kessler. (1993) Molecular genetics and biology of the bovine placental prolactin family. In: Trophoblast Cells: Pathways for Maternal-Embryonic Communication. M.J. Soares, S. Handwerger, and F. Talamantes, eds. Springer-Verlag, New York, pp. 191-205.

Scott, P., M.A. Kessler, and L.A. Schuler. (1992) Molecular cloning of the bovine prolactin receptor and distribution of prolactin and growth hormone receptor transcripts in fetal and uteroplacental tissues. Molecular and Cellular Endocrinology 89:47-58.