2006 Fiscal Year Final Research Report Summary
Signal transduction of chondroitin sulfate proteoglycans and neuronal network formation
| Project/Area Number |
17500268
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Neurochemistry/Neuropharmacology
|
|---|
| Research Institution | Tokyo Metropolitan Organization for Medical Research |
|---|
Principal Investigator |
MAEDA Nobuaki Tokyo Metropolitan Organization for Medical Research, Tokyo Metropolitan Institute for Neuroscience, Laboratory Head, 東京都神経科学総合研究所, 副参事研究員 (90202308)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
ISHII Maki Tokyo Metropolitan Organization for Medical Research, Tokyo Metropolitan Institute for Neuroscience, Research Associate, 東京都神経科学総合研究所, 研究員 (50415535)
HATA Toshihiro Tokyo Metropolitan Organization for Medical Research, Tokyo Metropolitan Institute for Neuroscience, Research Associate, 東京都神経科学総合研究所, 研究員 (30370977)
KANEKO Mika Tokyo Metropolitan Organization for Medical Research, Tokyo Metropolitan Institute for Neuroscience, Research Associate, 東京都神経科学総合研究所, 研究員 (00323163)
|
|---|
| Project Period (FY) |
2005 – 2006
|
| Keywords | Chondroitin sulfate / Proteoglycan / Cerebellum / Pleiotrophin / Tyrosine phosphorylation |
|---|
| Research Abstract |
PTPζ, a receptor-type protein tyrosine phosphatase, uses a heparin-binding growth factor pleiotrophin as a ligand and play important roles in the morphogenesis of cerebellar Purkinje cells. In this study, we studied functional interaction between PTPζ and DNER, a Delta/Notch-like receptor highly expressed in Purkinje cells. PTPζ and DNER displayed patchy co-localization in the dendritic shafts of Purkinje cells and in the COS-7 transfectants expressing both proteins. Immunoprecipitation experiments indicated that PTPζ and DNER formed complex both in vivo and in vitro. Several tyrosine residues in the intracellular region of DNER including the ones in and adjacent to the tyrosine-based sorting motif were phosphorylated, and were easily dephosphorylated by the PTPζ catalytic domain. The tyrosine-based sorting motif played critical roles in the endocytosis and intracellular transport of DNER, and tyrosine phosphorylation and destruction of this motif resulted in the accumulation of DNER on the plasma membrane of the PTPζ-expressing cells. Accumulation of DNER on the plasma membrane of Neuro-2A cells led to the morphological changes including extension of processes. Pleiotrophin suppressed the endocytosis of DNER and DNER-induced inhibition of neurite outgrowth of Neuro-2A cells. These observations suggests that pleiotrophin-PTPζ signaling regulates the morphogenesis of Purkinje cells by modifying the intracellular transport of DNER.
|
