Faculty Talks with Kenneth L. Madsen’s group

Following a summer vacation, we present the next Neuroscience.rocks seminar featuring Kenneth Lindegaard Madsen together with his two PhD students Thorvald Faurschou Andreassen and Simon Erlendsson.

Wednesday, August 19 at 16:00 in the Faculty Club

Program

  • 16:00: Kenneth will give an introduction to scaffolding proteins in the post synaptic density and synaptic plasticity.
  • 16:20: Thorvald will be speaking about “Investigating Cellular Activity and protein trafficking in Dissociated Neuronal Cultures fluorescent biosensors”.
  • 16:35: Simon will talk about Molecular scaffolding from the inside out – using inverted membrane sheets to quantitatively probe scaffolding.

After the talks, refreshments will be served. Please share the word with your collegues. We are looking forward to seeing you all there.

Kenneth L. Madsen’s group

Research
Our research addresses fundamental aspects of basic pharmacology, molecular pharmacology and neuropharmacology, with certain potential translational parts. We aim to better understand neuronal cell biology with particular focus on protein trafficking and signalling processes in the synthetic and endocytic pathway as well as molecular interactions with expert knowledge on, protein-lipid interactions as well as protein-protein interactions.

Work Package 1 is focused on the pharmacology of PSD95/Disc-large/ZO-1 homology (PDZ) mediated proteins-protein interaction and how these domains might represent new attractive pharmacological targets as alternatives to surface receptors.

Work Package 2 will seek to explore the controversial idea that trafficking of receptors and transporters, which in many cases is strongly integrated with their pharmacology, is determined not only by protein-protein interactions, but also by yet unappreciated protein-lipid interactions that govern localization of the receptors and transporters to areas of high membrane curvature in the plasma membrane.

Work Package 3 is aimed at obtaining fundamental new understanding of dopamine signaling processes in the brain. Evidently, this has broad pharmacotherapeutic perspectives given the key role of dysfunctional dopamine signaling in many brain disease including schizophrenia, bipolar disorder, ADHD, Parkinsons’ Disease and drug abuse.

Methodologies
Molecular biology, protein purification, receptor binding, advanced light microscopy, including live microscopy and fluorescence energy transfer microscopy (FRET), trafficking assays of integral membrane proteins using ELISA and confocal microscopy.

For further information, visit Kenneth L. Madsen’s INF-website.

Relevant publications
Karlsen ML, Thorsen TS, Johner N, Ammendrup-Johnsen I, Erlendsson S, Tian X, Simonsen JB, Høiberg-Nielsen R, Christensen NM, Khelashvili G, Streicher W, Teilum K, Vestergaard B, Weinstein H, Gether U, Arleth L, Madsen KL. Structure of Dimeric and Tetrameric Complexes of the BAR Domain Protein PICK1 Determined by Small-Angle X-Ray Scattering. Structure. 2015.

Erlendsson S, Rathje M, Heidarsson PO, Poulsen FM, Madsen KL, Teilum K, Gether U. ‘PICK1 (protein interacting with C-kinase 1) binding promiscuity relies on unconventional PDZ (PSD-95/Discs-large/ZO-1 homology) binding modes for non-class II PDZ ligands’. JBC 2014.

Rathje M, Fang H, Bachman JL, Anggono V, Gether U, Huganir RL, Madsen KL. AMPA receptor pHluorin-GluA2 reports NMDA receptor-induced intracellular acidification in hippocampal neurons. Proc Natl Acad Sci U S A. 2013.

Holst B, Madsen KL, Jansen AM, Jin C, Rickhag M, Lund VK, Jensen M, Bhatia V, Sørensen G, Madsen AN, Xue Z, Møller SK, Woldbye D, Qvortrup K, Huganir R, Stamou D, Kjærulff O, Gether U. PICK1 deficiency impairs secretory vesicle biogenesis and leads to growth retardation and decreased glucose tolerance. PLoS Biol. 2013.

Madsen KL, Thorsen TS, Rahbek-Clemmensen T, Eriksen J, Gether U. Protein Interacting with C Kinase 1 (PICK1) Reduces Reinsertion Rates of Interaction Partners Sorted to Rab11-dependent Slow Recycling Pathway. J Biol Chem. 2012.

Thorsen TS*, Madsen KL*, Rebola N, Bach A, Moreira I, Peters D, Dyhring T, Beuming T, Stuhr-Hansen N, Mulle C, Weinstein H, Strømgaard K, Rønn LC and Gether U. Identification of a small molecule inhibitor of the PICK1 PDZ domain that inhibits synaptic plasticity. Proc Natl Acad Sci U S A. 2010.