title: Caspr4 interaction with LNX2 modulates the proliferation and neuronal differentiation of mouse neural progenitor cells.
abstract: Contactin-associated protein 4 (Caspr4), also known as contactin-associated protein-like protein (CNTNAP4), is expressed in various regions of the brain. Recent reports suggest that CNTNAP4 is a susceptibility gene of autism spectrum disorders (ASDs). However, the molecular function of Caspr4 in the brain has yet to be identified. In this study, we show an essential role of Caspr4 in neural progenitor cells (NPCs). Caspr4 is expressed in NPCs in the subventricular zone (SVZ), a neurogenic region in the developing cortex. Knocking down of Caspr4 enhances the proliferation of NPCs derived from the SVZ of embryonic day 14 mouse. Neuronal differentiation is increased by overexpression of Caspr4, but decreased by knocking down of Caspr4 in cultured mouse NPCs. Transfection of the intracellular domain of Caspr4 (C4ICD) rescues the abnormal decreased neuronal differentiation of Caspr4-knocking down NPCs. Ligand of Numb protein X2 (LNX2), a binding partner of Numb, interacts with Caspr4 in a PDZ domain-dependent manner and plays a similar role to Caspr4 in NPCs. Moreover, transfection of LNX2 rescues the decreased neuronal differentiation in Caspr4-knocking down NPCs. In contrast, transfection of C4ICD fails to do so in LNX2-knocking down NPCs. These results indicate that Caspr4 inhibits neuronal differentiation in a LNX-dependent manner. Therefore, this study reveals a novel role of Caspr4 through LNX2 in NPCs, which may link to the pathogenesis of ASDs.
authors.affiliation: 1 Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and Institute of Neuroscience, Soochow University , Suzhou, China .
authors.forename: Feng-Ting
authors.initials: FT
authors.lastname: Yin
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Futagawa
authors.forename: Di
authors.initials: D
authors.lastname: Li
authors.forename: Yan-Xia
authors.initials: YX
authors.lastname: Ma
authors.forename: Mei-Hong
authors.initials: MH
authors.lastname: Lu
authors.forename: Li
authors.initials: L
authors.lastname: Lu
authors.forename: Shen
authors.initials: S
authors.lastname: Li
authors.forename: Yao
authors.initials: Y
authors.lastname: Chen
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Cao
authors.forename: Zara Zhuyun
authors.initials: ZZ
authors.lastname: Yang
authors.forename: Shigeru
authors.initials: S
authors.lastname: Oiso
authors.forename: Kentaro
authors.initials: K
authors.lastname: Nishida
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kuchiiwa
authors.forename: Kazutada
authors.initials: K
authors.lastname: Watanabe
authors.forename: Katsushi
authors.initials: K
authors.lastname: Yamada
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Takeda
authors.forename: Zhi-Cheng
authors.initials: ZC
authors.lastname: Xiao
authors.forename: Quan-Hong
authors.initials: QH
authors.lastname: Ma
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000502:physiology*; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000502:physiology*; D058953:Neural Stem Cells / Q000502:physiology*; D054731:PDZ Domains
chemical_list: D002352:Carrier Proteins; C464568:Cntnap4 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; C454301:Lnx2 protein, mouse; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins