BBB seminar: Donald Gullberg
Why do vertebrates have collagen receptors?
Hovedinnhold
Donald Gullberg
Division for Physiology, Department of Biomedicine, University of Bergen
Integrins are heterodimeric cell adhesion receptors that are evolutionary conserved. We have identified the latest member of the integrin family α11β1, orthologues of which exists in zebrafish but not in Drosophila (1). We have shown that α11β1 is a collagen receptor that is expressed in a subset of mesenchymal cells (2,3). In recent years much has been learned about integrin function using transgenic techniques. To study the potential function of α11 for mesenchymal tissue formation and integrity we generated a null allele of the α11 gene. α11 knockout mice are viable and fertile, but display dwarfism and succumb to malnutrition with increased mortality. We have recently shown that α11 -/- mice have severely defective incisors with disorganised periodontal ligaments and disturbed teeth structure. In the mutant periodontal ligaments the cell and collagen organisation is disturbed whereas in teeth dentin and enamel production are both dysregulated. Studies of α11β1-defective embryonic fibroblasts in vitro indicate defects in cell adhesion to collagen I, a reduced ability of cells to reorganise fibrillar collagens and reduced cell proliferation. Our data support a model where α11β1 integrin plays a fundamental role in collagen reorganisation in the periodontal ligament; thus, α11 integrin mutations might be involved in periodontal disease and other diseases affecting teeth. We are currently interbreeding different strains of knockout mice to obtain animals lacking several types of collagen receptors.
1. Velling, T., Kusche-Gullberg, M., Sejersen, T., and Gullberg, D. (1999) J. Biol.Chem. 274, 25735-25742
2. Tiger, C.-F., Fougerousse, F., Grundström, G., Velling, T., and Gullberg, D. (2001) Dev. Biol. 237, 116-129
3. Popova, S., Rodriguez-Sanchez, B., Barrzcyk, M., Tiger, C., Lu, N., Aszodi, A., Thesleff, I., Forsberg, E., and Gullberg, D. (2004) Dev. Biol. in press
Donald Gullberg was appointed as professor at the Department of Biomedicine, UoB, in January 2004. He obtained his Ph.D. at the Department of Medical Chemistry, Uppsala University, in 1990 on a thesis dealing with the characterisation of collagen receptors. 1990-1992 he did a postdoc with John and Lisa Fessler at UCLA on a project involving the role of integrins during muscle development in Drosophila melanogaster. In 1993 he returned to Uppsala and started his own research group in the Department of Animal Physiology and received a 6 year position financed by the Swedish Medical Research Council. During this period the latest member of the integrin family (α11β1) was identified in cultured muscle cells in his research group. Later the cDNA was cloned, the gene was mapped and more recently a knockout mouse lacking integrin α11 protein was produced in his laboratory. A cell line stably expressing α11-EGFP chimera has been produced in his laboratory. At the moment his research group is working on understanding the molecular mechanism underlying the observed knockout phenotype. Further characterisation of the promoter with the aim of producing transgenic mice with promoter-reporter constructs are ongoing as well as interbreeding of the integrin α11 deficient mice with other knockout mice of the integrin family. |