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Abstract
Receptor-type protein tyrosine phosphatase zeta/beta (RPTPzeta) is a transmembrane
chondroitin sulfate proteoglycan (CSPG) and has been shown to play crucial roles in
controlling axonal growth and neuronal migration. The RPTPzeta has two transmembranous
isoforms, shorter receptor form of RPTPzeta (sRPTPzeta) and full-length receptor form
of RPTPzeta (fRPTPzeta), but no studies have been reported about functional difference
of these two isoforms. In the present study, therefore, we examined whether or not
two RPTPzeta isoforms have different role in controlling dendritic morphology and
synaptic number in cultured hippocampal neurons using the quantitative morphometrical
analysis. Confocal microscopic observation showed that the immunoreactivity of RPTPzeta
was observed throughout cells such as axons, growth cones, and dendrites at the early
stages of neuronal culture, while it was seen predominantly on dendrites at the late
stages. Western blotting analysis revealed that fRPTPzeta was mainly expressed at
the early stages of culture and both RPTPzeta isoforms were expressed at late stages
of culture. The overexpression of sRPTPzeta in hippocampal neurons increased the dendritic
arborization without altering the average length of dendritic branches, whereas that
of fRPTPzeta decreased the dendritic arborization and increased the average length
of dendritic branches. The RNA interference of fRPTPzeta expression increased the
dendritic arborization without altering the average length of dendritic branches.
The overexpression of fRPTPzeta decreased the density of hippocampal dendritic synapses,
but that of sRPTPzeta had no effects. Pleiotrophin, a ligand for RPTPzeta to interfere
the phosphatase activity, increased the density of hippocampal dendritic synapses.
Thus, the present study demonstrates that two transmembranous RPTPzeta isoforms have
different functions for regulating dendritogenesis and synaptogenesis.