Faculty

Biochemistry and Molecular Genetics Faculty.

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Contact Information

University Of Illinois at Chicago

Dept. Of Biochemistry and

Molecular Genetics

900 S. Ashland (M/C 669)
Chicago, IL 60607
tel: 312-996-7670
fax: 312-413-0353

Dr. Karen Colley

karenc@uic.edu

Major Interests:

The overall goal of my research program is to understand how the process of glycoprotein glycosylation is controlled and how attached oligosaccharide structures influence the biological function of the proteins that they modify. As carbohydrate structures are now appreciated to play important roles in mediating and modulating cell interactions during development, disease and in the normal cell, these questions have taken on increased importance. The laboratory studies a family of glycosyltransferases called the sialyltransferases that add terminal sialic acid to glycoproteins and glycolipids.


Dr. Karen. J. Colley, Professor Ph.D. 1987, Washington University, St. Louis Postdoctoral studies University of California, Los Angeles

We have two main projects in laboratory:

The Signals and Mechanisms Mediating Glycosylation Enzyme Localization in the Golgi. The glycosylation enzymes that terminally modify protein- and lipid-linked oligosaccharides are localized in specific cisterna of the Golgi stack. This compartmentation enhances the efficiency of the glycosylation process by concentrating the glycosyltransferases with their sugar nucleotide donors, which are imported from the cytosol, and their glycoconjuate substrates, which are made in the same or preceeding cistena. To study the signals and mechanisms involved in the Golgi protein localization, we have used the a2, 6-sialyltransferase of Asn-linked protein glycosylation as our model system. We have elucidated the sequences of the sialyltransferase required for its Golgi localization and shown that the ability to form detergent insoluble oligomers correlates with the stable localization of one sialyltransferase isoform. Currently, we are pursuing studies to elucidate the mechanisms involved in maintaining the steady state localization of the sialyltransferase and other late Golgi glycosyltransferases. Our goal is to understand the role that two proposed trafficking and localization models play in the localization of these glycosylation enzymes. The vesicular transport model suggests that Golgi proteins are retained in specific cisternae, while the cisternal maturation model suggests that continued retrograde transport leads to the maintenance of glycosylation enzymes in the Golgi.

The Vescular Transport Model of Protein Transport through Golgi

Golgi proteins are retained in the cisternae

The Cisternal Maturation Model of Protein Transport Through Golgi

Golgi proteins are
retained in the cisternae
by continuous retrograde
transport in COPII
coated vesicles

The Molecular Basis for the Protein Specific Polysialylation of Neural Cell Adhesion Molecule (NCAM).
Long chains of a2, 8-linked polysialic acid have been demonstrated to negatively modulate NCAM-dependent and –independent cell adhesion, and be critical for axon guidance and cell migration during development. Unlike most glycosylation events, the addition of polysialic acid is a protein specific event. It is found on the oligosaccharides of only four mammalian proteins including NCAM, the a subunit of the voltage dependent sodium channel, and the polysialyltransferases, PST and STX. The major goal of this project is to determine the NCAM sequence or structural motifs that allow PST and STX to specifically recognize and polysialylate this protein's oligosaccharides. In addition, we have found that the presence of polysialic acid on PST and STX appears to impact the amount of polysialic acid added to NCAM. We are currently evaluating how this may occur, and how the enzymes polysialylate their own oligosaccharides. Our future studies will include evaluating the role of polysialylated PST and STX as anti-adhesives during metastasis, and how polysialic acid may act as both a pro-adhesive agent and an anti-adhesive agent in different cellular environments.

NCAM Domain Structure
and Sites of Glycosylation/
Polysialation

Model of
Polysialytransferase-
NCAM Interactions

Publications:

Ma, J., Qian, R., Rausa, F. M., and Colley, K. J. (1997) Two forms of the sialyltransferase differing by a single amino acid in their catalytic domains are processed differently by cells. J. Biol. Chem. 272, 672-679.

Close, B. E. and Colley, K. J. (1998) In vivo autopolysialylation and localization of the polysialyltransferases PST and STX. J. Biol. Chem. 273, 34586-34593.

Kitazume-Kawaguchi, S., Dohmae, N., Takio, K., Tsuji, S. and Colley, K. J. (1999) The relationship between ST6Gal I Golgi retention and its cleavage-secretion. Glycobiology 9, 1397-1406.

Close, B. E. and Colley, K. J. (2000) PST Autopolysialylation is not requisite for polysialylation of NCAM. J. Biol. Chem. 275, 4484-4491.

Chen, C. and Colley, K. J. (2000) Minimal structural and glycosylation requirements for ST6Gal I activity and trafficking. Glycobiology 10, 531-538.

Chen, C., Lazic, A., Backovic, M., Ma, J. and Colley, K. J. (2000) Formation of insoluble oligomers correlates with ST6Gal I stable localization in the Golgi,. J. Biol. Chem. 275, 13819-13826.

Qian, R., Chen, C. and Colley, K. J. (2001) Location and mechanism of ST6Gal I dimer formation: Role of cysteine residues in enzyme dimerization, localization, activity and processing. J. Biol. Chem. 276, 28641-28649.

Close, B. E., Wilkinson, J. M., Bohrer T. J., Goodwin, C. P., Broom L. J., and Colley, K. J. (2001) The polysialyltransferase ST8Sia II/STX: Post-translational processing and role of autopolysialylation in the polysialylation of neural cell adhesion molecule. Glycobiology 11, 997-1008.

Chen, T.-L., L., Chen, C., Bergeron, N. Q., Close, B. E., Bohrer, T. J., Vertel, B. M., and Colley, K. J. (2002) The two rat a2, 6-sialyltransferase (ST6Gal I) isoforms: Evaluation of catalytic activity and intra-Golgi localization. Glycobiology, in press.