It has been reported that the fusion protein with the protein transduction
domain (PTD) peptide of HIV-I Tat protein can be internalized through the c
ell membrane of intact cells, although the exact mechanism is unknown. In t
his report. we investigated whether this new method could be used for the m
olecular analysis of exocytosis via HPC-1/syntaxin 1A, which plays an impor
tant role in transmitter release. When applied to PC12 cells, Tat PTD fusio
n proteins were rapidly internalized into most cells. In order to show that
the internalized protein remained biologically active, the H3 domain of HP
C-1/syntaxin 1A was fused to Tat PTD (Tat-H3). Transmitter release in PC12
cells was suppressed by Tat-H3 treatment. These results indicate that the T
ar fusion protein is a useful tool for analyzing the process of transmitter
release. (C) 2001 Elsevier Science B.V. All rights reserved.