Role of axons in the regulation of PO biosynthesis by Schwann cells

Abstract

The role of axons in the expression of the major myelin glycoprotein, P0, has been investigated using neuron/Schwann cell cultures. These cultures were either nonmyelinating or myelinating due to growth in defined medium or in medium containing serum and chick embryo extract, respectively. The neurons and Schwann cells used in the studies were derived from embryonic day 15 rat dorsal root ganglia (DRG), and the Schwann cells from these ganglia are shown not to synthesize appreciable levels of P0 prior to growth in culture. Myelinating cultures of Schwann cells and neurons grown together for 18-21 days synthesize P0 that is readily identified by immunoblotting. The nonmyelinating cultures, which do not assemble basal lamina, also synthesize P0 that is detectable by either [3H]mannose precursor incorporation or by immunoblotting. The steady-state level of P0 in the nonmyelinating cultures is less than that of the myelinating cultures, and the P0 that is synthesized by the former appears to be catabolized shortly after its biosynthesis. Since nonmyelinating Schwann cells synthesize P0 when in contact with neurites in vitro, we have examined the ability of such nonmyelinating cells to express the glycoprotein in vivo. Very little steady-state P0 is detected in immunoblots of the adult rat cervical sympathetic trunk (CST), a nerve in which approximately 99% of the axons are nonmyelinated. Similarly, the amounts of [3H]mannose and [3H]amino acids that are incorporated into newly synthesized P0 are much lower in the CST than in the adult sciatic nerve.(ABSTRACT TRUNCATED AT 250 WORDS)