N-Acetylated alpha-linked acidic dipeptidase may be involved in axon Schwann cell signalling

N-Acetylated alpha-linked acidic dipeptidase is a membrane-bound peptidase that cleaves the neuropeptide N-acetyl-aspartyl-glutamate to N-acetyl-aspartate and glutamate. Previously, we have shown that in adult rat this enzyme is expressed by the non-myelinating Schwann cells in peripheral nerve. In the present study, we have determined the expression pattern of this peptidase in rat sciatic nerve during late embryonal and early postnatal development, using double-label immunofluorescence, enzyme assays and immunoblotting. We demonstrate that N-acetylated alpha-linked acidic dipeptidase is expressed by all Schwann cell precursor cells on embryonal day 14/15 and by all undifferentiated Schwann cells on embryonal days 16/17 and 20/21 and postnatal day 1. Moreover, we show that during the first postnatal week, the peptidase expression is down-regulated in the myelinating Schwann cells while the total enzyme activity levels and the enzyme amounts present in the nerve are transiently increased. To determine whether Schwann cell peptidase expression is dependent on axonal contact, we performed immunofluorescence experiments in cultured Schwann cells. These in vitro experiments demonstrate that the expression of this enzyme is maintained in culture for several weeks without axonal contact. Furthermore, they confirm previous suggestions that this peptidase is expressed on the extracellular side of the Schwann cell membrane. These findings support the notion that N-acetylated alpha-linked acidic dipeptidase takes part in signaling between peripheral axons and Schwann cells. The temporary increase in peptidase activity during the first postnatal week strongly implicates a role for this enzyme in the process of axon ensheathment and/or axon myelination.