A chondroitin sulfate proteoglycan PTPzeta /RPTPbeta regulates the morphogenesis of Purkinje cell dendrites in the developing cerebellum.
PTPzeta/RPTPbeta, 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-PTPzeta 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 PTPzeta, (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-PTPzeta 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-PTPzeta signaling regulates the morphogenesis of Purkinje cell dendrites and that the mechanisms underlying that regulation involve the GLAST activity in Bergmann glial processes.
Tanaka
Masahiko
M
Division of Cell Biology, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi 470-1192, Japan. mtanaka@fujita-hu.ac.jp
Maeda
Nobuaki
N
Noda
Masaharu
M
Marunouchi
Tohru
T
D027322:Amino Acid Transport System X-AG / Q000032:analysis / Q000502:physiology; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology; D002478:Cells, Cultured; D002531:Cerebellum / Q000254:growth & development* / Q000378:metabolism; D011508:Chondroitin Sulfate Proteoglycans / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism / Q000502:physiology; D003712:Dendrites / Q000201:enzymology / Q000648:ultrastructure*; D008959:Models, Neurological; D009024:Morphogenesis; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000502:physiology*; D009457:Neuroglia / Q000737:chemistry / Q000166:cytology; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism / Q000502:physiology*; D011689:Purkinje Cells / Q000166:cytology / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5
D027322:Amino Acid Transport System X-AG; D002352:Carrier Proteins; D011508:Chondroitin Sulfate Proteoglycans; D016207:Cytokines; D009419:Nerve Tissue Proteins; C066845:pleiotrophin; D017027:Protein Tyrosine Phosphatases; C516897:Ptprz1 protein, rat; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5