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PRODID:-//Columba Systems Ltd//NONSGML CPNG/SpringViewer/ICal Output/3.3-
 M3//EN
VERSION:2.0
CALSCALE:GREGORIAN
METHOD:PUBLISH
BEGIN:VEVENT
DTSTAMP:20150306T123227Z
DTSTART:20150310T130000Z
DTEND:20150310T140000Z
SUMMARY:"Molecular mechanisms of Repulsive Guidance Molecules (RGMs) in B
 MP and Neogenin signalling – from cell migration to morphogen regulation
 "
UID:{http://www.columbasystems.com/customers/uom/gpp/eventid/}l11k-i55hrx
 nd-d1trsu
DESCRIPTION:Part of the Tissue Systems seminar series.                   
                                                                         
                                                                         
                                                                         
                                                                         
                                                  \n\nABSTRACT\n\nRepulsi
 ve Guidance Molecules (RGMs) were initially identified and named for the
 ir ability to repel neurons grown from chicken retinas. We now know that
  the three RGM family members control a large and diverse range of cellu
 lar functions\, from immune cell regulation (RGMA)\, to cell motility (R
 GMB)\, and iron homeostasis (RGMC). Due to their numerous roles\, abnorm
 al RGM function or expression has been linked to various diseases includ
 ing multiple sclerosis\, cancer and blood diseases. RGMs are tethered to
  the outside of the plasma membrane where they function to mediate cruci
 al cell-to-cell communication in the extracellular matrix. RGMs can sign
 al by binding directly to the cell surface guidance receptor Neogenin (N
 EO1) a member of the immunoglobulin super family and an paralogue of the
  Netrin receptor DCC (Deleted in Colorectal Cancer)\, but also act as ac
 tivators of Bone Morphogenetic Protein (BMP) signalling\, a fundamental 
 morphogen pathway in development.\n\nDespite numerous genetic and functi
 onal studies\, the molecular mechanisms underlying extracellular RGM rec
 eption and signal transduction still remain poorly understood. Here\, I 
 present you structural and functional data on RGM complexes with NEO1\, 
 suggesting a mechanism by which two RGM molecules act as a molecular sta
 ple\, bringing together the juxtamembrane regions of two NEO1 receptors\
 , thus resulting in downstream signalling and actin cytoskeleton rearran
 gements important for the RGM-mediated function in processes of cell mig
 ration. Furthermore\, our molecular analysis on RGM complexes with the B
 MP ligand BMP2\, together with biophysical and cellular experiments\, su
 ggest a mechanism for RGM-mediated activation of BMP signalling that is 
 dependent on pH and cellular localisation\, and offers a molecular ratio
 nale for RGM mutations causing the blood disease juvenile hemochromatosi
 s (JHH). Finally\, the crystal structure of a ternary BMP-NEO1-RGM compl
 ex\, supported by solution scattering data and quantitative super-resolu
 tion microscopic clustering analysis\, provides direct evidence of a phy
 sical link between the NEO1 and BMP pathways bridged by RGMs\, thus putt
 ing forward an important new mechanism for cellular signalling.\n       
               
STATUS:TENTATIVE
TRANSP:TRANSPARENT
CLASS:PUBLIC
LOCATION:Lecture Theatre\, Michael Smith Building\, Manchester
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