Analysis of receptor-like transmembrane proteins expressed in neurons

2004 Fiscal Year Final Research Report Summary

• Project/Area Number: 15500252
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Tohoku University
• Principal Investigator: TOHGO Akira Tohoku University, Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 助手 (40282123)
• Project Period (FY): 2003 – 2004
• Keywords: DNER / Knockout mouse / Cerebellum / GLAST / Purkinje cell

Research Abstract

Delta/Notch-like EGF-related Receptor (DNER) is a transmembrane protein strongly expressed in cerebellar Purkinje cells (PCs), and thought to contribute to the functional communication via cell-cell interaction based on its unique structural feature. To clarify its function in the cerebellum, we have generated mice with a targeted gene disruption of DNER. The knockout mice exhibited motor discoordination in fixed bar and rota-rod tests. Histological observation found retardation in cerebellar morphogenesis and persistent abnormalities in a fissure. Electrophysiological analyses revealed that mutant PCs retained multiple innervations from climbing fibers (CFs) even at young adult stages. Moreover, synaptic transmission from parallel fibers (PFs) or CFs to PCs was apparently normal, but the uptake of glutamate released at the PF-PC synapses was significantly reduced in the knockout mice. Western blot analysis indicated reduced expression levels of GLAT in mutant cerebella. These results indicate that DNER is essential for maturation of neural circuitry, and also suggest that DNER mediates functional interactions between PCs and BG/CF.