| Autor: |
Chowdhury MIH; Department of Cell Pharmacology, Nagoya University., Nishioka T; Department of Cell Pharmacology, Nagoya University., Mishima N; Department of Cell Pharmacology, Nagoya University., Ohtsuka T; Department of Biochemistry, Yamanashi University., Kaibuchi K; Department of Cell Pharmacology, Nagoya University.; Institute for Comprehensive Medical Science, Fujita Health University., Tsuboi D; Institute for Comprehensive Medical Science, Fujita Health University. |
| Jazyk: |
angličtina |
| Zdroj: |
Cell structure and function [Cell Struct Funct] 2020 Sep 01; Vol. 45 (2), pp. 143-154. Date of Electronic Publication: 2020 Jul 08. |
| DOI: |
10.1247/csf.20028 |
| Abstrakt: |
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.Key words: Prickle2, Igsf9b, axon initial segment, neuronal excitability, ASD. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
