BEGIN:VCALENDAR VERSION:2.0 PRODID:-//Talks.cam//talks.cam.ac.uk// X-WR-CALNAME:Talks.cam BEGIN:VEVENT SUMMARY:Should I Stick Or Should I Go? A molecular switch at the neuronal surface - A. Radu Aricescu\, PhD MRC Senior Research Fellow\, University o f Oxford Wellcome Trust Centre for Human Genetics DTSTART:20140422T130000Z DTEND:20140422T140000Z UID:TALK52170@talks.cam.ac.uk CONTACT:Ingo Greger DESCRIPTION:Receptor protein tyrosine phosphatase sigma (RPTPσ\;)\, wh ich regulates neuronal extension through interactions with proteoglycans\, has recently emerged as a presynaptic nexus for multiple protein and prot eoglycan interactions during synaptogenesis. Mechanisms governing the shif t in RPTPσ\; function from outgrowth promotion and its subsequent abil ity to act as a synaptic organizer are\nunknown. Crystallographic and elec tron microscopic analyses of the RPTPσ\; ectodomain reveal an\nextensi ve inter-domain flexibility. Furthermore\, a crystal structure of RPTP` 3\; in complex with the postsynaptic receptor protein tyrosine kinase TrkC details an interaction surface partially overlapping the previously chara cterized proteoglycan-binding site suggesting competition between presynap tic proteoglycans and postsynaptic TrkC. Accordingly\, heparin oligomers i nhibit RPTPσ\;:TrkC interaction in vitro and disrupt TrkC-dependent sy naptic differentiation. Various lines of\nevidence converge towards a mode l whereby transient emergence of the RPTPσ\; ectodomain from the presy naptic proteoglycan layer allows capture by TrkC to form a trans-synaptic complex\, the consequent reduction in RPTPσ\; flexibility potentiating interactions with additional postsynaptic ligands to orchestrate excitato ry synapse formation. LOCATION:MRC LMB - Sanger Seminar room END:VEVENT END:VCALENDAR