Involvement of fatty acid synthase in axonal development in mouse embryos.

BACKGROUND: Dynamic protein palmitoylation of signalling proteins is thought to be an important step in the regulation of signal transduction in eukaryotic cells. The enzyme responsible for protein palmitoylation in vertebrates, however, has not been identified. I have previously reported that p260/270, which is expressed in embryos of the silkworm Bombyx mori, has protein palmitoylase activity.
RESULTS: A homologue of Bombyx p260/270, mouse fatty-acid synthase (FAS), was shown to be expressed specifically throughout most of the central and peripheral nervous system in mouse embryos. Mouse FAS was expressed specifically in cultured primary neurones in which growth-associated protein (GAP)-43 was expressed. GAP-43, by protein palmitoylation, regulates Go signal transduction and neural axonal growth. In a cell-free system, purified FAS from mouse embryos transferred palmitate to GAP-43 through cysteine residues. Furthermore, cerulenin, an inhibitor of FAS, reduced axonal growth and in vivo palmitoylation of GAP-43 in cultured neurones.
CONCLUSIONS: Mouse FAS was hypothesized to be responsible for the palmitoylation of GAP-43 and subsequent regulation of axonal growth in mouse embryos.