Our lab investigates the compartmentalisation of stress-activated protein kinase (SAPK) pathway function in neuronal systems. It has recently become appreciated that JNK pools can be organised in the cell into discrete complexes by so-called scaffold proteins. Overexpression studies suggest that these proteins bind only specific upstream members of the JNK MAPK cascade providing some level of selectivity, and their co-association enhances signalling from MAPK kinase kinase (MEKK) to MAPK kinase to MAPK. In addition the scaffold can localise a pool of kinases to specific regions of the cell, and in yeast they are known to confer specific functions to the associated kinases. Therefore scaffold proteins, some of which are themselves MEKKs, can potentially organise total cellular MAPK activity into functionally distinct pools. Our lab has recently obtained evidence that stable multiprotein "scaffolded" JNK-pathway complexes genuinely exist in neuronal systems in the absence of over-expression. We aim to determine the distribution of SAPK activity and SAPK activation capacity among scaffold proteins in brain and neuronal cultures, the constituents of these complexes and their function. This information may permit the design of more specific drugs to treat neurodegenerative diseases.