The largest isoform of Ankyrin-G is required for lattice structure of the axon initial segment

Wang，Yiming1; Guan，Meiling2; Wang，Han1; Li，Yu1; Zhanghao，Karl4; Xi，Peng2,4; Zhang，Yan1,3

2021-11-12

10.1016/j.bbrc.2021.09.017

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   影响因子和分区

0006-291X

1090-2104

Alzheimer's disease (AD) is the most frequent neurodegenerative disease and a common dementia in elderly individuals. Previous studies found a strong correlation between axon initial segment (AIS) defects and AD, but it remains unclear whether AD itself changes the arrangement of AIS components, and the mechanisms by which adaptor proteins and ion channels in the AIS are disturbed in AD are not well understood. With super-resolution structured illumination microscopy (SIM) revealing axonal structures, here we imaged the lattice structure of completely assembled AIS in APP/PS1 neurons. By analyzing the images with Gaussian fitting and 1D mean autocorrelation, we found dual spacings (∼200 nm and ∼370 nm) of Ankyrin-G (AnkG), Na1.2 and βIV-spectrin in AD model APP/PS1 mice due to the low-expressed 480-kDa AnkG. To identify the roles of each AnkG isoform, two isoforms were separately expressed in neurons from AnkG conditional knockout mice. Mice rescued with 270-kDa AnkG displayed dual spacings of AnkG components in cultured neurons and impaired in spatial memory, while transgenic mice expressing 480-kDa AnkG showed a normal molecular distribution in the AIS and normal cognitive performance. Our findings provide new insight into the mechanisms underlying impaired cognition associated with neurodegenerative diseases such as AD.

Alzheimer's disease Ankyrin-G Axon initial segment Structured illumination microscopy

SCI

英语

其他

WOS:000697493700003

BIOLOGY & BIOCHEMISTRY

2-s2.0-85114929830

Scopus

1.State Key Laboratory of Membrane Biology,College of Life Sciences,Peking University,Beijing,100871,China
2.Department of Biomedical Engineering,College of Future Technology,Peking University,Beijing,100871,China
3.PKU-IDG/McGovern Institute for Brain Research,Peking University,Beijing,100871,China
4.UTS-SUStech Joint Research Centre for Biomedical Materials & Devices,Department of Biomedical Engineering,College of Engineering,Southern University of Science and Technology,Shenzhen,518055,China

Wang，Yiming,Guan，Meiling,Wang，Han,et al. The largest isoform of Ankyrin-G is required for lattice structure of the axon initial segment[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2021,578:28-34.

Wang，Yiming.,Guan，Meiling.,Wang，Han.,Li，Yu.,Zhanghao，Karl.,...&Zhang，Yan.(2021).The largest isoform of Ankyrin-G is required for lattice structure of the axon initial segment.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,578,28-34.

Wang，Yiming,et al."The largest isoform of Ankyrin-G is required for lattice structure of the axon initial segment".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 578(2021):28-34.