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Séminaire impromptu - Kenneth Lindegaard MadsenMembrane modulating BAR domain proteins in regulation of budding from the Golgi complex during biogenesis of dense core vesicles

Abstract :

Secretory vesicles in endocrine cells store peptide hormones such as growth hormone (GH) and insulin before their release into the bloodstream. The molecular mechanisms governing budding of immature secretory vesicles from the trans-Golgi network (TGN) and their subsequent maturation remain unclear. This talk will discuss the recent findings that a subfamily of BAR domain proteins, including PICK1, ICA69 and Arfaptin1, play a key role in the early stages of dense core vesicle biogenesis, with focus on the dimeric PICK1/ICA69 complex. Our efforts range from understanding the underlying molecular mechanisms, involving recognition and generation of membrane curvature, to the physiological role of these proteins investigated in mice and flies. Finally, we show recent evidence that mutations in PICK1 are associated with metabolic syndrome in humans patients.

 

Selected publications

PICK1 deficiency impairs secretory vesicle biogenesis and leads to growth retardation and decreased glucose tolerance. 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.  PLoS Biol. 2013;11(4)

Rathje M, Fang H, Bachman JL, Anggono V, Gether U, Huganir RL, Madsen KL (2013) AMPA receptor pHluorin-GluA2 reports NMDA receptor-induced intracellular acidification in hippocampal neurons. Proc Natl Acad Sci U S A 110:14426-14431.

Madsen KL, Thorsen TS, Rahbek-Clemmensen T, Eriksen J, Gether U (2012) Protein interacting with C kinase 1 (PICK1) reduces reinsertion rates of interaction partners sorted to Rab11-dependent slow recycling pathway. J Biol Chem 287:12293-12308.

 

 

Agenda des séminaires

Cursus

2013- Associate professor, Molecular Neuropharmacology group. Department of Pharmacology and Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen

2010-13: Post Doc, Molecular Neuropharmacology group. Professor, M.D. Ulrik Gether, at Department of Pharmacology and Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen. Fellowship from FSS

Jan 2010 Paternity leave (3 months)

2008-10: Post Doc, Molecular Neuropharmacology group, funded by KU Programme of Excellence in ‘Biomolecular scaffolding of neurotransmitter transporters and receptors’.