Contributed Lecture
Structure and Function of the srGAP Neuronal Migration Factors

The migration of neurons determines the structure and connectivity of the nervous system. During this process, the leading edges of migrating neurons are re-shaped continuously as a concert of extracellular and intracellular signals transduce information to cytoskeleton and membrane-remodeling proteins. Defects in this process have been implicated directly in human disorders of sensation, cognition and motor skills. The srGAP family of proteins regulates the migration and morphology of neurons by coupling and coordinating remodeling reactions of the neuronal membrane and the cytoskeleton in response to several stimuli from neighboring cells in developing neural networks. It was discovered recently that some srGAP isoforms are unique to humans and have played a major role in evolution of the large and highly evolved human neocortex. Similar isoforms are found in some types of cancers and in human patients suffering from schizophrenia. Despite such fundamental importance, we do not have a clear mechanistic understanding of srGAP’s remarkable properties. We study the biochemical and structural properties of srGAP proteins versus srGAPs implicated in human evolution and disease. For that, we use X-ray crystallography, biochemical and biophysical methods. Our results shed light on the fundamental roles that srGAPs play during human development and disease.