Peder Madsen

Peder Madsen
Associate professor
More information  

RESEARCH
The Vps10p-D receptors (or sortilins) constitute a family of five type one receptors. The receptors are expressed in many tissues but are particularly abundant in the system, notably in the brain. Each receptor contains a unique ten-bladed b-propeller at the N-terminus, and a conserved central tunnel in the b-propeller harbors binding sites for a variety of ligands, including neurotrophic proteins and peptides as well as soluble and transmembrane receptors.  The short intracellular part of the receptors comprise several consensus motifs for binding of different types of cytoplasmic interactors. Two of the receptors are differentially spliced giving rise to receptors with several different cytoplasmic amino acid sequences.

By now it is clear that the sortilins are truly multifunctional. They modulate the signaling and turnover of several neurotrophic factors, they mediate sorting and intracellular transport of target proteins, and deficiency in one or more of the receptors seems associated with neurologic and mental disorders like ADHD and Alzheimers Disease. However, the underlying mechanisms and the full functional capacity of the sortilins are still largely unknown, and need further clarification.

RESEARCH INTERESTS
Molecular, cellular and physiological functions of the Vps10p-domain receptors, with particular focus on Sortilin and SorLA .

Identification of new ligands (soluble and transmembrane); Vps10p-domain structure; implications of receptor:ligand complex formation on protein structure and cellular functions; receptor trafficking; identification and characterization of cytosolic interactors and their possible role in the machinery that governs receptor sorting and signaling.

METHODOLOGIES
Studies of Vps10p-D receptors in tissue and cultured wild-type cells, and in transfected and untransfected cell-lines; ‘Large scale’ affinity-purification of receptors from tissues and cell cultures;

Studies of protein:protein interactions using Surface Plasmon Resonance (BIAcore), Isothermal Titration Calorimetry (ITC200) and yeast two-hybrid; sub-cellular fractionation and gradient centrifugation; immuno-fluorescence microscopy, including ‘high content screening and live-imaging; yeast two-hybrid screening of cDNA libraries.

COLLABORATORS & Centers

  • The MIND center
  • Claus Munck Petersen,  Anders Nykjær, Morten Nielsen, Camilla Gustafsen, Lone Tjener Pallesen, Simon Glerup, Mads Kjølby, Olav Andersen, Christian Vægter, Karen Marie Petersen, Kimmo Jensen, Department of Biomedicine
  • Jens Nyengaard, Department of Clinical Medicine, AU
  • Søren Thirup, Jacob Lauwring , Poul Nissen, Department of Molecular Biology and Genetics AU
  • Mart Sarma, University of Helsinki, Finland
Henvendelse om denne sides indhold: 
Revideret 03.08.2016