Evidence that a major site of expression of the RHO-GTPASE activating protein, oligophrenin-1, is peripheral myelin

Oligophrenin-1 is a recently discovered Rho-GTPase activating protein, mutation of which is associated with X-linked mental retardation. Since little is known about the cellular localization of oligophrenin-1 in central and peripheral neurons, we investigated its expression by RT-PCR and immunochemical analysis. Oligophrenin-1 immunoreactivity was found in glial cells forming myelin sheaths in the vagus nerve, sciatic nerve and dorsal roots of guinea-pig, rat and human, in chromaffin cells of the adrenal medulla, and in chromaffin cells associated with sympathetic ganglia. No immunoreactivity was detected in sympathetic neurons, in glial cells surrounding these neurons, in optic nerve or in spinal cord myelin. The full length cDNA sequence was determined from guinea-pig sciatic nerve. The translated amino acid sequence was 99% identical to the published human oligophrenin-1 sequence. Western blotting revealed two protein forms which were expressed to different relative extents in different tissues. A 91 kDa form was predominant in extracts of sciatic nerve whereas a 36 kDa form was relatively more abundant in adrenal medulla and brain. Greater amounts of the full length oligophrenin-1 protein occurred in the sciatic nerve of adult rats, compared with P2 rats, which reflects the development of myelination. The presence of multiple forms does not appear to be due to alternative mRNA splicing since RT-PCR products amplified from a variety of tissues were identical and only a single mRNA transcript of 7.4 kb was identified by Northern analysis. These findings demonstrate that a major site of oligophrenin-1 expression is peripheral myelin.