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The Journal of Neuroscience, April 1, 2003, 23(7):2804
A Chondroitin Sulfate Proteoglycan PTP /RPTP Regulates the
Morphogenesis of Purkinje Cell Dendrites in the Developing Cerebellum
Masahiko
Tanaka1,
Nobuaki
Maeda2, 3,
Masaharu
Noda2, and
Tohru
Marunouchi1
1 Division of Cell Biology, Institute for Comprehensive
Medical Science, Fujita Health University, Toyoake, Aichi 470-1192, Japan, 2 National Institute for Basic Biology, Graduate
University for Advanced Studies, Okazaki, Aichi 444-8585, Japan, and
3 Tokyo Metropolitan Institute for Neuroscience, Fuchu,
Tokyo 183-8526, Japan
PTP /RPTP , a receptor-type protein tyrosine phosphatase
synthesized as a chondroitin sulfate (CS) proteoglycan, uses a
heparin-binding growth factor pleiotrophin (PTN) as a ligand, in which
the CS portion plays an essential role in ligand binding. Using an
organotypic slice culture system, we tested the hypothesis that
PTN-PTP signaling is involved in the morphogenesis of Purkinje cell
dendrites. An aberrant morphology of Purkinje cell dendrites such as
multiple and disoriented primary dendrites was induced in slice
cultures by (1) addition of a polyclonal antibody against the
extracellular domain of PTP, (2) inhibition of protein tyrosine
phosphatase activity, (3) enzymatic removal of the CS chains, (4)
addition of exogenous CS chains, and (5) addition of exogenous PTN, all of which disturb PTN-PTP signaling. These treatments also reduced the immunoreactivity to GLAST, a glial glutamate transporter, on
Bergmann glial processes. Furthermore, a glutamate transporter inhibitor also induced the abnormal morphogenesis of Purkinje cell
dendrites. Altogether, these findings suggest that PTN-PTP signaling
regulates the morphogenesis of Purkinje cell dendrites and that the
mechanisms underlying that regulation involve the GLAST activity in
Bergmann glial processes.
Key words:
PTP/RPTP; pleiotrophin; GLAST; Purkinje cell; dendritic morphogenesis; cerebellum; organotypic slice culture
Copyright © 2003 Society for Neuroscience 0270-6474/03/2372804-11$05.00/0
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