NOVEL DOMAIN-SPECIFIC ACTIONS OF AMYLOID PRECURSOR PROTEIN ON DEVELOPING SYNAPSES

The effect of the secretory form of amyloid precursor protein (sAPP) o n synaptic transmission was examined by using developing neuromuscular synapses in Xenopus cell cultures. The frequency of spontaneous posts ynaptic currents (SSCs) was reduced by the addition of sAPP, whereas t he amplitude of impulse-evoked postsynaptic currents (ESCs) was increa sed by sAPP. These opposing effects on spontaneous versus evoked relea se were separated by using the specific domain of APP. The C-terminal fragment of sAPP (CAPP) only reduced SSC frequency and did not affect ESCs. By contrast, the N-terminal fragment of sAPP (NAPP) did not affe ct SSC frequency but did increase ESC amplitude. The reduction of SSC frequency by sAPP appears to be mediated by activation of potassium ch annels through a cGMP-dependent pathway, whereas the increase of ESC a mplitude is mediated by a different pathway involving activation of pr otein kinase(s). These results suggest the potential role of sAPP as a modulator of synaptic activity by two specific domains.