title: Localization of nectin-2δ at perivascular astrocytic endfoot processes and degeneration of astrocytes and neurons in nectin-2 knockout mouse brain.
abstract: Nectins are Ca2+-independent immunoglobulin-like cell-cell adhesion molecules. In the nervous system, among four members (nectin-1, -2, -3, and -4), nectin-1 and -3 are asymmetrically localized at puncta adherentia junctions formed between the mossy fiber terminals and the dendrites of CA3 pyramidal neurons in the mouse hippocampus and heterophilic trans-interactions between nectin-1 and nectin-3 are involved in the selective interaction of axons and dendrites of cultured neurons. By contrast, nectin-2, which has two splicing variants, nectin-2α and -2δ, has not been well characterized in the brain. We showed here that nectin-2α was expressed in both cultured mouse neurons and astrocytes whereas nectin-2δ was selectively expressed in the astrocytes. Nectin-2δ was localized at the adhesion sites between adjacent cultured astrocytes, but in the brain it was localized on the plasma membranes of astrocytic perivascular endfoot processes facing the basement membrane of blood vessels. Genetic ablation of nectin-2 caused degeneration of astrocytic perivascular endfoot processes and neurons in the cerebral cortex. These results uncovered for the first time the localization and critical functions of nectin-2 in the brain.
authors.affiliation: Division of Signal Transduction, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; Division of Pathogenetic Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe 650-0047, Japan.
authors.forename: Muneaki
authors.initials: M
authors.lastname: Miyata
authors.affiliation: Division of Pathogenetic Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe 650-0047, Japan; CREST, Japan Science and Technology Agency, Kobe, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Mandai
authors.affiliation: Division of Pathogenetic Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe 650-0047, Japan; CREST, Japan Science and Technology Agency, Kobe, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Maruo
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Sato
authors.affiliation: Division of Pathogenetic Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe 650-0047, Japan; Department of Neurology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Shiotani
authors.affiliation: CREST, Japan Science and Technology Agency, Kobe, Japan; Department of Neural Regeneration and Cell Communication, Mie University Graduate School of Medicine, Tsu 514-8507, Japan.
authors.forename: Aika
authors.initials: A
authors.lastname: Kaito
authors.affiliation: CREST, Japan Science and Technology Agency, Kobe, Japan; Department of Neural Regeneration and Cell Communication, Mie University Graduate School of Medicine, Tsu 514-8507, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Itoh
authors.affiliation: CREST, Japan Science and Technology Agency, Kobe, Japan; Department of Neural Regeneration and Cell Communication, Mie University Graduate School of Medicine, Tsu 514-8507, Japan.
authors.forename: Shujie
authors.initials: S
authors.lastname: Wang
authors.affiliation: CREST, Japan Science and Technology Agency, Kobe, Japan; Department of Neural Regeneration and Cell Communication, Mie University Graduate School of Medicine, Tsu 514-8507, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Fujiwara
authors.affiliation: CREST, Japan Science and Technology Agency, Kobe, Japan; Department of Neural Regeneration and Cell Communication, Mie University Graduate School of Medicine, Tsu 514-8507, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Mizoguchi
authors.affiliation: Division of Pathogenetic Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe 650-0047, Japan; CREST, Japan Science and Technology Agency, Kobe, Japan. Electronic address: ytakai@med.kobe-u.ac.jp.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Takai
authors.affiliation: Division of Signal Transduction, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; CREST, Japan Science and Technology Agency, Kobe, Japan; Department of Medical Pharmaceutics, Kobe Pharmaceutical University, Kobe 658-8558, Japan. Electronic address: rikitake@kobepharma-u.ac.jp.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Rikitake
keywords: Adhesion molecule; Astrocytes; Blood brain barrier; Endfoot; Nectin, Afadin