Neurotrophic factors and their receptors

........................................................................................................12 1. LITERATURE REVIEW...............................................................................14 1.1 NEUROTROPHIC FACTORS ....................................................................................14 1.2 THE GDNF FAMILY OF NEUROTROPHIC FACTORS .................................................17 1.3 THE GDNF FAMILY RECEPTORS AND SIGNALLING ................................................20 1.3.1 Ligand Binding Coreceptor..........................................................................21 1.3.2 Receptor tyrosine kinase RET......................................................................22 1.3.3 GFL-GFR -RET interaction ........................................................................23 1.3.4 RET signalling.............................................................................................25 1.3.5 Alternative signalling modes of GDNF........................................................28 1.3.6 Lipid rafts in GDNF signalling ....................................................................30 1.3.7 Heparan sulphate in GDNF signalling..........................................................30 1.4 MANF AND CDNF FAMILY OF NEUROTROPHIC FACTORS .....................................33 1.4.1 MANF as a neurotrophic factor....................................................................33 1.4.2 CDNF as a neurotrophic factor ....................................................................34 1.4.3 MANF and CDNF in the ER........................................................................36 1.4.4 Saposins and SAPLIPs.................................................................................37 1.5 DISEASES RELATED TO GDNF-RET SIGNALLING AND MANF/CDNF...................39 1.5.1 Knockout studies in GDNF-GFR 1-RET system.........................................39 1.5.2 RET mutations.............................................................................................39 1.5.3 GDNF in Parkinson’s disease ......................................................................41 1.5.4 MANF/CDNF in Parkinson’s disease ..........................................................43 2. AIMS OF THE STUDY.................................................................................44 3. METHODS....................................................................................................45 Methods used in studies I-III....................................................................45