Membrane trafficking in enterocytes
Our longstanding main research interest is the small intestine, in particular the absorptive cells (enterocytes). Generated in the proliferative regions of the crypts of Lieberkühn, enterocytes migrate upwards to the tip of the villi from where they are extruded into the gut lumen after a life-span of only 3-6 days. Within this period, they rapidly differentiate into mature cells in preparation for their main function: to digest and assimilate nutrients from the diet. A key element in this process is to generate and maintain an extensive luminal brush border membrane capable of acting as a digestive/absorptive surface as well as a permeability barrier against luminal pathogens. In addition, enterocytes are continuously engaged in transcytosis of IgA, providing local, luminal immunity. Together, these functions require a complex network of apical membrane trafficking routes in which a subapical endosomal compartment may serve as a central hub interconnecting the brush border, the TGN, the basolateral cell surface, and lysosomes.
It is well known that sphingolipids and cholesterol together form microdomains (commonly termed "lipid rafts") in the exoplasmic leaflet of cell membranes. Rafts are thought to exist as ordered membrane patches surrounded by more fluid membrane mainly composed of glycerolipids. In the enterocyte glycolipids make up a large fraction of the brush border membrane, where cross-linking lectins, such as members of the galectin family, stabilize lipid rafts. This robust membrane organization enables the brush border to withstand the harsh working environment prevailing in the lumen of the gut.
Current Project Areas
Using a variety of polar- and lipophilic probes, we are exploring the endocytic membrane dynamics of the brush border using organ cultured mucosal explants as an in vivo-like model system. Amongst the recent project areas are epithelial interactions with enterotoxins and immunoglobulin trafficking. Currently, we are investigating the interaction of various permeation enhancers with the intestinal epithelium to gain insight into the mechanisms whereby these compounds may facilitate absorption of oral drugs across the gut epithelial barrier.
Collectively, more than half our working hours is dedicated to teaching mainly within the course programs in cell biology (GHH) and biochemistry (EMD) offered by the Faculty to pregraduate medical, odontology, molecular biomedicine, human biology, and biomedical engineering students. All types of teaching, including lectures, class-room teaching, live-streaming and lab practicals are provided. Preparing- and executing exams semiannually is also a major task with >800 students signing up for these courses annually.
- Danielsen EM, Hansen GH. Intestinal surfactant permeation enhancers and their interaction with enterocyte cell membranes in a mucosal explant system. Tissue Barriers. 2017 Jul 3;5(3):e1361900.
- Danielsen ET, Danielsen EM. Glycol chitosan: A stabilizer of lipid rafts in the intestinal brush border. Biochim Biophys Acta. 2017 Mar;1859(3):360-367.
- Michael Danielsen E, Hansen GH. Small molecule pinocytosis and clathrin-dependent endocytosis at the intestinal brush border: Two separate pathways into the enterocyte. Biochim Biophys Acta. 2016 Feb;1858(2):233-43.
- Danielsen EM, Hansen GH. Generation of stable lipid raft microdomains in the enterocyte brush border by selective endocytic removal of non-raft membrane.
PLoS One. 2013 Oct 4;8(10):e76661.
- Hansen GH, Rasmussen K, Niels-Christiansen LL, Danielsen EM. Endocytic trafficking from the small intestinal brush border probed with FM dye. Am J Physiol Gastrointest Liver Physiol. 2009 Oct;297(4):G708-15.
- Danielsen EM, Hansen GH. Lipid raft organization and function in brush borders of epithelial cells. Mol Membr Biol. 2006 Jan-Feb;23(1):71-9. Review.
For funding our research, we are indebted to:
Læge Sofus Carl Emil Friis og hustru Olga Doris Friis Legat
Aase og Ejnar Danielsens Fond
Brødrene Hartmanns Fond
A. P. Møller og Hustru Chastine Mc-Kinney Møllers Fond