APBB1 stimulates Rac1-mediated neurite outgrowth by interacting with ELMO1
Refereed conference paper presented and published in conference proceedings

香港中文大學研究人員

其它資訊
摘要Background: Neurite damage is commonly observed in injured neurons of Alzheimer’s patients. Investigation on neurite outgrowth mechanism may provide insights for initiating neurite regeneration. Brain-enriched adaptor protein amyloid-beta A4 precursor protein-binding family B member 1 (APBB1), also known as FE65, is reported to stimulate neurite extension via Rac1 activation (Cheung, Dunbar et al. 2014). However, the mechanism for APBB1-mediated Rac1 activation remains elusive. Here, ELMO1 is identified as a novel APBB1 interactor to modulate Rac1-dependent neurite extension.
Methods:Characterization of APBB1-ELMO1 interactions was done by various biochemical assays. To study the effect of APBB1-ELMO1 interaction in neurite outgrowth and Rac1 activation, measure of the longest neurite in transfected primary cortical neurons and Rac1 activation assay were performed. Additionally, the effect of APBB1-ELMO1 interaction in ELMO1 autoinhibitory configuration was investigated by GST pulldown assay and proximity ligation assay. Furthermore, plasma membrane isolation and immunofluorescence were performed to study the relationship between APBB1 and ELMO1 plasma membrane targeting.
Results: APBB1 N-terminal region interacts with ELMO1. Both neurite outgrowth and Rac1 activation were potentiated by their interaction. Disrupting their interaction with APBB1 mutant attenuates such stimulatory effects. Upon binding with APBB1, ELMO1 releases its autoinhibitory conformation. Moreover, APBB1-ELMO1 interaction facilitate the plasma membrane targeting of ELMO1.
Conclusions: APBB1 stimulate neurite extension through Rac1 activation by interacting with ELMO1 to release its autoinhibitory conformation and facilitate its plasma membrane targeting.
出版社接受日期31.05.2019
著者CHAN Wai Wa Ray, LI Wen, LAU Kwok Fai
會議名稱International Alzheimer’s Disease Conference 2019
會議開始日31.05.2019
會議完結日01.06.2019
會議地點Hong Kong
會議國家/地區香港
會議論文集題名International Alzheimer’s Disease Conference 2019
出版年份2019
月份5
出版地Hong Kong
文章號碼8
頁次35 - 35
語言英式英語
關鍵詞APBB1, FE65, neurite outgrowth

上次更新時間 2019-13-06 於 14:29