SEMINAR

Membrane complexes in the brush-border membrane and their role in protein nutrition

Abstract
Transport of neutral amino acids in epithelial cells of the intestine and proximal tubules of the kidney is mediated by a heteromeric complex of the membrane transporter B0AT1 and its ancillary proteins angiotensin-converting enzyme 2 (Ace2) in the intestine and collectrin in the kidney. Ace2 and collectrin are required for surface expression and functional activation of the transporter complex. Deletion of the transporter in mice improves glycaemic control and provides resistance against diet-induced obesity. Homology models of B0AT1 based on the prokaryotic leucine transporter LeuT provide a basis to analyse the interaction of B0AT1 with collectrin and to design novel inhibitors as a potential novel treatment of type 2 diabetes.

References
1. Jiang, Y., Rose, A. J., Sijmonsma, T. P., Broer, A., Pfenninger, A., Herzig, S., Schmoll, D., and Broer, S. (2015) Mice lacking neutral amino acid transporter B(0)AT1 (Slc6a19) have elevated levels of FGF21 and GLP-1 and improved glycaemic control. Mol Metab 4, 406-417

2. Fairweather, S. J., Broer, A., Subramanian, N., Tumer, E., Cheng, Q., Schmoll, D., ML, O. M., and Broer, S. (2015) Molecular basis for the interaction of the mammalian amino acid transporters B0AT1 and B0AT3 with their ancillary protein collectrin. The Journal of biological chemistry

BIOGRAPHY

2008-present: Professor, Research School of Biology, Australian National University
2006-2008: Associate Professor, School of Biochemistry and Molecular Biology, Australian National University
2000-2006: Senior Lecturer, School of Biochemistry and Molecular Biology, Australian National University
1998-2000: Senior Lecturer, Institute of Physiology, University of Tübingen
1993-1998: Junior Lecturer, Institute of Physiological Chemistry, University of Tübingen
1991-1993: Postdoctoral Fellow, University of Illinois, Chicago
1991: PhD Biochemistry, University of Düsseldorf

Research Fields and Interest:
Membrane transporters are essential to move hydrophilic nutrients across cellular membranes. We are particularly interested in the role of amino acid transporters in epithelial barriers and in cancer cells. Membrane transporters are highly flexible molecules that can switch topology to expose binding sites to both sides of the membrane. We are investigating structural and functional aspects of amino acid transporters as targets to treat type 2 diabetes and cancer.

Selected publications:
1. Jiang, Y., Rose, A. J., Sijmonsma, T. P., Broer, A., Pfenninger, A., Herzig, S., Schmoll, D., and Broer, S. (2015) Mice lacking neutral amino acid transporter B(0)AT1 (Slc6a19) have elevated levels of FGF21 and GLP-1 and improved glycaemic control. Mol Metab 4, 406-417

2. Fairweather, S. J., Broer, A., Subramanian, N., Tumer, E., Cheng, Q., Schmoll, D., ML, O. M., and Broer, S. (2015) Molecular basis for the interaction of the mammalian amino acid transporters B0AT1 and B0AT3 with their ancillary protein collectrin. The Journal of biological chemistry

3. Tumer, E., Broer, A., Balkrishna, S., Julich, T., and Broer, S. (2013) Enterocyte-specific regulation of the apical nutrient transporter SLC6A19 (B(0)AT1) by transcriptional and epigenetic networks. The Journal of biological chemistry 288, 33813-33823

4. Fairweather, S. J., Broer, A., O'Mara, M. L., and Broer, S. (2012) Intestinal peptidases form functional complexes with the neutral amino acid transporter B(0)AT1. Biochem J 446, 135-148

5. Broer, A., Juelich, T., Vanslambrouck, J. M., Tietze, N., Solomon, P. S., Holst, J., Bailey, C. G., Rasko, J. E., and Broer, S. (2011) Impaired Nutrient Signaling and Body Weight Control in a Na+ Neutral Amino Acid Cotransporter (Slc6a19)-deficient Mouse. J Biol Chem 286, 26638-26651

6. Kowalczuk, S., Broer, A., Tietze, N., Vanslambrouck, J. M., Rasko, J. E., and Broer, S. (2008) A protein complex in the brush-border membrane explains a Hartnup disorder allele. Faseb J 22, 2880-2887