Prickle2 and Igsf9b coordinately regulate the cytoarchitecture of the axon initial segment

Md Imrul Hasan Chowdhury, Tomoki Nishioka, Noriko Mishima, Toshihisa Ohtsuka, Kozo Kaibuchi, Daisuke Tsuboi

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)143-154
Number of pages12
JournalCell Structure and Function
Issue number2
StatePublished - 2020
Externally publishedYes


  • ASD
  • Axon initial segment
  • Igsf9b
  • Neuronal excitability
  • Prickle2

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology


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