We examined effects of phorbol esters on the amount and the subcellular dis
tribution of the activity-regulated protein Vesl-1S/ Homer-la in cultured h
ippocampal neurons. Major Vesl-1S immunoreactivity (IR) was detected throug
hout neuronal somata under control conditions. Bath application of phorbol
esters, PMA and PDBU resulted in the increase in the amount of Vesl-1S prot
eins and promoted punctate distribution of Vesl-1S IR at the cortical regio
ns of the neuronal somata. Immunofluorescent observations using antisynapto
physin and anti-Vesl-1S antibodies, and electron microscopic observations,
revealed that Vesl-1S accumulated at postsynaptic regions following PMA app
lication. Membrane depolarization with high concentrations of external pota
ssium also promoted the punctate distribution of Vesl-1S IR. These results
demonstrate that phorbol-triggered reaction cascades result in the accumula
tion of Ves-1S protein at postsynaptic regions, and suggest that these phor
bol effects may mimic those caused by synaptic activities.