Isoprenylation of brain 2',3'-cyclic nucleotide 3'-phosphodiesterase modulates cell morphology

CNP (2,3'-cyclic nucleotide 3'-phosphodiesterase) is the earliest myelination specific polypeptide to be synthesized by oligodendrocytes (OLs). When non-myelinating "naive" cells are transfected with the rat CNP cDNA, CNP accumulates intracellularly in a punctate manner, as well as at the plasma membrane. Filopodia and processes, like those of OLs become elongated and more numerous, and are filled with this protein. Post-translational isoprenylation of the terminal C-T-I-I sequence with either farnesyl or geranylgeranyl is essential for this phenomenon. In contrast, the non-isoprenylated C397S mutant is homogeneously distributed throughout the cytoplasm and does not markedly affect cellular morphology. We have synthesized CNP and the C397S mutant in vitro and have shown that isoprenylation is essential for the binding of newly synthesized CNP to myelin.