Widespread distribution of the c-src gene product in nerve cells and axon terminals in the adult rat brain

Abstract

The regional and cellular distribution of the proto-oncogene product pp60c-src, a member of the family of membrane-associated tyrosine-specific protein kinases, was analysed in adult rat brain. High-resolution SDS-PAGE allowed analysis of both the 'fibroblast' 60-kDa form and a variant, 61-kDa neuron-specific form of the c-src gene product which is encoded by an alternately processed c-src mRNA. Studies of microdissected brain regions showed that all CNS regions contained both forms of the enzyme, the 61-kDa form predominating in most regions with high content of gray matter and high density of synapses. Lesion-induced degenerations of specific neuronal elements in the basal ganglia decreased the level of both forms of the c-src gene product both in regions where cell bodies had been lesioned and in regions where nerve terminals had degenerated. The 61-kDa form of the enzyme appeared somewhat more sensitive to the effects caused by these lesions than the 60-kDa form. These results indicate that, within the mature mammalian brain, both cell body regions and nerve terminals of many, and possibly all, nerve cells contain both forms of the c-src gene product, the 61-kDa form being most highly enriched in the nerve cells. These results suggest that the enzyme may be involved in pleiotropic functions, including signal transduction in nerve terminals.