@article{c45e8f86913d4cdfb59d242e466cb99e,
title = "Prickle2 and Igsf9b coordinately regulate the cytoarchitecture of the axon initial segment",
abstract = "Prickle2 has been identified in genetic studies of subjects with autism spectrum disorder (ASD) and epilepsy, but the pathological mechanism of Prickle2 remains to be fully understood. Proteomic analysis of Prickle2 with mass spectrometry revealed twenty-eight Prickle2 interactors, including immunoglobulin superfamily member 9b (Igsf9b), in the brain. Here, because Igsf9 family proteins are associated with psychiatric diseases and seizures, we studied the physiological interaction between Prickle2 and Igsf9b. Prickle2 colocalized with Igsf9b in cultured hippocampal neurons. Knockdown of Prickle2 affected the subcellular localization of Igsf9b. Interestingly, Igsf9b localized along axonal processes in a pattern opposite to the ASD-related molecule ANK3/AnkG. AnkG is a major component of the axon initial segment (AIS), where a variety of ASD and epilepsy susceptibility proteins accumulate. Igsf9b-knockdown neurons displayed altered AnkG localization. Prickle2 depletion caused defects in AnkG and voltage-gated Na+ channel localization, resulting in altered network activity. These results support the idea that Prickle2 regulates AnkG distribution by controlling the proper localization of Igsf9b. The novel function of Prickle2 in AIS cytoarchitecture provides new insights into the shared pathology of ASD and epilepsy.",
keywords = "ASD, Axon initial segment, Igsf9b, Neuronal excitability, Prickle2",
author = "Chowdhury, {Md Imrul Hasan} and Tomoki Nishioka and Noriko Mishima and Toshihisa Ohtsuka and Kozo Kaibuchi and Daisuke Tsuboi",
note = "Funding Information: and conflict of interest disclosure. We thank Mr. Kentaro Taki, a member of the core staff of Nagoya University Equipment, for supporting the mass spectrometry experiment and Mr. Yamato Hida at Yamanashi University for supporting the immunohistochemical study. This work was supported by Grants-in-Aid for Scientific Research on Innovative Areas: {\textquoteleft}Constructive understanding of multiscale dynamism of neuropsychiatric disorders (19142160){\textquoteright}, grants-in-aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan (KAKENHI grant numbers: JP19142160, JP17921988), a grant-in-aid for “Integrated research on neuropsychiatric disorders” carried out under the Strategic Research Program for Brain Sciences from AMED (grant No. 19dm0207075h0001), and a grant-in-aid from the Hori Sciences & Arts Foundation (FV2019). The authors declare that they have no conflicts of interest. Funding Information: Kentaro Taki, a member of the core staff of Nagoya University Equipment, for supporting the mass spectrometry experiment and Mr. Yamato Hida at Yamanashi University for supporting the immunohistochemical study. This work was supported by Grants?in?Aid for Scientific Research on Innovative Areas: {\textquoteleft}Constructive understanding of multiscale dynamism of neuropsychiatric disorders (19142160){\textquoteright}, grants?in?aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan (KAKENHI grant numbers: JP19142160, JP17921988), a grant?in?aid for “Integrated research on neuropsychiatric disorders” carried out under the Strategic Research Program for Brain Sciences from AMED (grant No. 19dm0207075h0001), and a grant?in?aid from the Hori Sciences & Arts Foundation (FV2019). The authors declare that they have no conflicts of interest. Publisher Copyright: {\textcopyright} 2020 The Author(s).",
year = "2020",
doi = "10.1247/csf.20028",
language = "English (US)",
volume = "45",
pages = "143--154",
journal = "Cell Structure and Function",
issn = "0386-7196",
publisher = "Japan Society for Cell Biology",
number = "2",
}