Identification of active regions for neurite outgrowth activity of neurocrescin

We previously identified and cloned a neurite outgrowth promoting protein, Neurocrescin (NC), from the extract of the chick denervated leg muscles. In this study, we explored the active region of NC for neurite outgrowth. Usi ng the deletion mutants of NC, we tested their neurite outgrowth activity i n the cultured telencephalic neurons of E5 chick embryos. We found three re gions which independently had significant neurite outgrowth activity compar able with that of the extract of the chick denervated leg muscles. These re gions were not homologous to any well-known active sites such as the lamini n active region, IKVAV. In parallel, searching the endogenous deletion muta nts of NC in the rat brain, we cloned a mutant in which the region includin g the larger part of one of the three active regions was deleted. The neuri te outgrowth activity of the mutant was significantly lower than that of no rmal NC. These results suggest the physiological significance of these acti ve regions. (C) 2001 Academic Press.