Polysialyltransferase ST8Sia II (STX) polysialylates all of the major isoforms of NCAM and facilitates neurite outgrowth

The neural cell adhesion molecule (NCAM) has different isoforms due to diff erent sizes in its polypeptide and plays a significant role in neural devel opment. In neural development, the function of NCAM is modified by polysial ylation catalyzed by two polysialyltransferases, ST8Sia II and ST8Sia IV. P reviously, it was reported by others that ST8Sia II polysialylates only tra nsmembrane isoforms of the NCAM, such as NCAM-140 and NCAM-180, but not NCA M-120 and NCAM-125 anchored by a glycosylphosphotidylinositol. In the prese nt study, we first discovered that ST8Sia II polysialylates all isoforms of the NCAM examined, and we demonstrated that polysialylation of NCAM expres sed on 3T3 cells facilitates neurite outgrowth regardless of isoforms of NC AM, where polysialic acid is attached. We then show that neurite outgrowth is significantly facilitated only when polysialylated NCAM is present in ce ll membranes. Moreover, the soluble NCAM coated on plates did not have an e ffect on neurite outgrowth exerted by soluble L1 adhesion molecule coated o n plates. These results, taken together, indicate that ST8Sia II plays crit ical roles in modulating the function of all major isoforms of NCAM. The re sults also support previous studies showing that a signal cascade initiated by NCAM differs from that initiated by L1 molecule.