Formation of signalling complexes in the nervous system

PATTERSON, SEAN I.

Villa Giardino, Córdoba

Simposio; VII Taller Argentino de Neurociencias; 2005

International Society for Neurochemistry

Many aspects of nervous system development and function depend on interactions between neural cells mediated by recognition of cell surface molecules and the subsequent activation of selected intracellular signaling pathways to bring about coordinated responses. Recent years have seen a massive increase in the identification of cell-surface and intracellular elements of such pathways, and the progressive documentation of interactions that allow crosstalk between pathways once thought to operate independently. Much effort is currently being directed towards defining how these pathways maintain specificity of action and a strong theme in such studies is the use of subcellular compartmentalization to restrict the number of possible interactions that a given protein may have. The compartmentalization of proteins within cells gives rise to signalling complexes whose composition can be dynamically regulated by multiple processes, usually involving either structural elements within proteins or covalent modification of the proteins (such as phosphorylation and lipidation). Protein interaction domains are a highly diverse group of transposable modules that provide specificity in interactions between proteins and with membranes. Such domains now number in the hundreds with more continuing to be found. Nonetheless, structural studies suggest that, despite lack of sequence homology, there may be common structural elements in many such domain families. Such studies also give us insight into how specificity can be maintained within families, giving rise to a very great number of potential specific interactions. In this symposium, we will cover some background regarding the molecular mechanisms underlying the formation of signaling complexes. This will be followed by descriptions of signaling complexes that form in the context of processes fundamental to growth and repair of the nervous system – specifically the involvement of (1) domain-containing scaffold proteins in neuromuscular synaptogenesis and (2) bi-directional signalling mediated by Thy-1 and integrins in the inhibition of regeneration in the mature spinal cord