INHIBITION OF AXONAL GROWTH BY BREFELDIN-A IN HIPPOCAMPAL-NEURONS IN CULTURE

The outgrowth of neuronal processes involves a great increase in the s urface area of the cell. The supply of membrane material necessarily m ust be coordinated with the demands for neurite growth. The selective growth of only one or two neurites al any given time during the develo pment of polarity raises the possibility that the production of materi als by the soma is limiting for growth (Dotti and Banker, 1987; Dotti et al., 1988; Goslin and Banker, 1990). To examine the role of the ava ilability of membrane components during the development of polarity an d axonal elongation, we treated neurons with brefeldin A, an antibioti c that disrupts the trafficking of vesicles from the Golgi complex to the plasma membrane. Treatment with brefeldin A (1 mu g/ml) inhibited axonal growth within 0.5 hr; in unpolarized cells it prevented the for mation of an axon. These results indicate that the availability of mem brane components of Golgi-derived vesicles is required for axonal grow th and hence the development of polarity. Inhibitors of protein and RN A synthesis also blocked axonal growth and the development of polarity , but over a much slower time course. This suggests that the full comp lement of proteins and mRNAs required for the initial development of p olarity is present for several hours before polarity is actually estab lished.