title: The C-terminal region of Reelin is necessary for proper positioning of a subset of Purkinje cells in the postnatal cerebellum.
abstract: In the normal cerebellum, Purkinje cells (PCs) are generated in a zone along the ventricular surface, migrate radially, and align to form a single-cell layer. However, in mice lacking the secreted protein Reelin or its downstream adaptor protein Dab1, the majority of PCs are located ectopically in the deep cerebellar mass. Nonetheless, how Reelin regulates migration and alignment of PCs remains incompletely understood. Reelin has a highly-conserved C-terminal region (CTR), which is required for its full activity. Here, we report an abnormality of the cerebellum in Reelin CTR-lacking knock-in (ΔC-KI) mice. In the ΔC-KI mice, cerebellar formation was largely normal, but some PCs in selected regions were found to be located ectopically and to frequently form clusters. Ectopic PCs contained a higher amount of Dab1 protein and functional Reelin receptors, including mainly very low-density lipoprotein receptor than correctly-aligned PCs. Decreasing Dab1 gene dosage exacerbated mislocalization of PCs and the cerebellar structure in Reelin ΔC-KI mice. These results indicate that ectopic PCs in ΔC-KI mice failed to receive sufficient Reelin signaling en route to their final destinations. Further, we also found that Reelin protein with intact CTR binds preferentially to PCs. Thus, it was suggested that the extent or quality of Reelin/Dab1 signaling that PCs require for correct positioning vary and that Reelin with intact CTR is required for that of a certain subset of PCs.
authors: Department of Biomedical Science, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan.
authors: Kota
authors: K
authors: Nakamura
authors: Department of Biomedical Science, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan.
authors: Mako
authors: M
authors: Beppu
authors: Department of Biomedical Science, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan.
authors: Kaori
authors: K
authors: Sakai
authors: Department of Biomedical Science, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan.
authors: Hayata
authors: H
authors: Yagyu
authors: Department of Biomedical Science, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan.
authors: Saori
authors: S
authors: Matsumaru
authors: Department of Biomedical Science, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan.
authors: Takao
authors: T
authors: Kohno
authors: Department of Biomedical Science, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan. Electronic address: mhattori@phar.nagoya-cu.ac.jp.
authors: Mitsuharu
authors: M
authors: Hattori
mesh_terms: D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D002531:Cerebellum / Q000254:growth & development / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011689:Purkinje Cells / Q000166:cytology*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011973:Receptors, LDL / Q000378:metabolism; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000378:metabolism*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D011973:Receptors, LDL; D000091042:Reelin Protein; C036053:VLDL receptor; C469363:reelin receptor; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases
keywords: Dab1; Purkinje cell; Reelin; knock-in mouse