Impaired neurite outgrowth of src-minus cerebellar neurons on the cell adhesion molecule L1

Abstract The nonreceptor tyrosine protein kinases pp60 c-src , p590 fyn , and pp62 c-yes are localized in growth cones of developing neurons, but their function is undefined. To determine whether these tyrosine kinases were capable of regulating substrate-dependent axon growth, cultures of cerebellar neurons from wild-type, src − , fyn − , and yes − mice were analyzed for neurite outgrowth on the neural cell adhesion molecule L1 or the extracellular matrix protein laminin. The rate of neurite extension on L1 was reduced in src − , but not in fyb − or yes − neurons. Neurite extension on laminin was unaltered in src − , fyn − , or yes − neurons, indicating that pp60 c-src , p59 fyn , or pp62 c-yes is not likely to participate in integrin-dependent axon growth. These results demonstrate that pp60 c-src is a component of the intracellular signaling pathway in L1-mediated axonal growth and suggest that Src-related nonreceptor tyrosine kinases may have distinct, non-redundant functions in the nervous system.