ISOPRENYLATION OF BRAIN 2',3'-CYCLIC NUCLEOTIDE 3'-PHOSPHODIESTERASE MODULATES CELL MORPHOLOGY

CNP (2',3'-cyclic nucleotide 3'-phosphodiesterase) is the earliest mye lination specific polypeptide to be synthesized by oligodendrocytes (O Ls). When non-myelinating ''naive'' cells are transfected with the rat CNP cDNA, CNP accumulates intracellularly in a punctate manner, as we ll as at the plasma membrane. Filopodia and processes, like those of O Ls become elongated and more numerous, and are filled with this protei n. Post-translational isoprenylation of the terminal C-T-I-I sequence with either farnesyl or geranylgeranyl is essential for this phenomeno n. In contrast, the non-isoprenylated C397S mutant is homogeneously di stributed throughout the cytoplasm and does not markedly affect cellul ar morphology. We have synthesized CNP and the C397S mutant in vitro a nd have shown that isoprenylation is essential for the binding of newl y synthesized CNP to myelin. (C) 1994 Wiley-Liss, Inc.