IN-VIVO NEURONAL SYNTHESIS AND AXONAL-TRANSPORT OF KUNITZ PROTEASE INHIBITOR (KPI)-CONTAINING FORMS OF THE AMYLOID PRECURSOR PROTEIN

We have shown previously that the amyloid precursor protein (APP) is s ynthesized in retinal ganglion cells and is rapidly transported down t he axons, and that different molecular weight forms of the precursor h ave different developmental time courses. Some APP isoforms contain a Kunitz protease inhibitor (KPI) domain, and APP that lacks the KPI dom ain is considered the predominant isoform in neurons. We now show that , among the various rapidly transported APPs, a 140-kDa isoform contai ns the KPI domain. This APP isoform is highly expressed in rapidly gro wing retinal axons, and it is also prominent in adult axon endings. Th is 14O-kDa KPI-containing APP is highly sulfated compared with other a xonally transported isoforms. These results show that APP with the KPI domain is a prominent isoform synthesized in neurons in vivo, and the y suggest that the regulation of protease activity may be an important factor during the establishment of neuronal connections.