AICD釋放對NMDA受體調節之ANKS1B轉位之影響

Abstract

ANKS1B是一個新近發現的蛋白質，在人體內目前已知道有三種不同長度胺基酸的異構物。在過去的研究中發現ANKS1B和PSD有交互作用，且NMDA受體受到NMDA刺激後，ANKS1B會轉位到細胞核，和卡侯氏體 (Cajal body) 結合，並且誘導蛋白質的產生，因此ANKS1B也許有傳遞突觸到細胞核訊息的功能。研究結果亦指出ANKS1B會和AICD有交互作用，因此這個蛋白質也叫做AIDA-1。有些報導指出AICD可以進入細胞核，所以AICD最近被認為在調節基因轉錄的過程中扮演重要的角色。在這裡我們想釐清ANKS1B與AICD的交互作用是否會影響ANKS1B進入細胞核。我們使用SH-SY5Y來做NMDA測試實驗，發現在第60秒時，ANKS1B幾乎全部在細胞核。當細胞預先處理DAPT 4小時，再加入NMDA測試，發現ANKS1B並不會轉位到細胞核。推測APP蛋白似乎可以抓住ANKS1B，避免ANKS1B進入細胞核，所以AICD的切割對於ANKS1B的轉位很重要；也許AICD會和ANKS1B一起進入細胞核。

A novel protein, ANKS1B, has three isoforms in human. Previous studies demonstrated that ANKS1B can bind to PSD, and upon NMDA receptors (NMDARs) stimulation, it would translocate to nucleus, bind to CBs, and induce protein synthesis. So ANKS1B may be a synapse-to-nucleus messenger and help to regulate protein synthesis. This protein is also named AICD associated protein-1 (AIDA-1) as it has been shown to interact with APP intracellular domain (AICD). AICD has recently been suggested to play an important role in transcriptional regulation, and some reports indicate that AICD could be transported into nucleus. Here we want to clarify whether the interaction of ANKS1B with AICD is involved in its nuclear translocation. In this study, we did NMDA treatment in the SH-SY5Y cell line and found when cell was treated 60 seconds, ANKS1B was almost in the nucleus. When SH-SY5Y was pre-treated gamma-secretase inhibitor (DAPT) for 4 hours, ANKS1B couldn’t tranlocate to nucleus. We propose that APP may have the function of anchor to catch ANKS1B to prevent into the nucleus, the cleavage of AICD is very important to the translocation of ANKS1B, and AICD and ANKS1B may co-transport into nucleus.