Synaptosomal actin interactome analysis in an Alzheimer's disease mouse model. (1st February 2022)

• Record Type: Journal Article
• Authors: Kommaddi, Reddy Peera; Haseena, P A; Verma, Aditi; Chandran, Mahesh; Jaleel, Abdul; Ravindranath, Vijayalakshmi
• Is Part Of: Alzheimer's & dementia. Volume 17(2021)Supplement 3
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-02-01
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.052841
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: Filamentous actin (F‐actin) is one of the major cytoskeleton proteins present in dendritic spines and it is an essential component for defining dendritic spine morphology. We have shown that synaptosomal F‐actin levels were significantly decreased in APP/PS1 mice as early as 1 month of age. The molecular mechanisms involved in F‐actin loss in synaptosomes, the underlying factors and the functional consequence involved needs to be elucidated. Synaptic neurotransmission and synaptic plasticity are dependent on the dynamic regulation of the actin through actin interacting and actin‐modulating proteins. F‐actin nanoarchitecture is regulated by several factors, such as reactive oxygen species and cofilin and others that are present in the dendritic spines. Yet, the key players and their role in synaptosomal F‐actin organization remains unknown. Here, we characterized actin interactome from F‐actin fractions prepared from synaptosomes from wild type and APP/PS1 male mice. Method: Synaptosomes, F‐actin and G‐actin fractions from synaptosomes were isolated from brain cortices of age matched wild type (WT) and APP/PS1 male mice. We performed immunoprecipitation of all these fractions using an anti‐actin polyclonal antibody and followed by LC‐MS/MS spectrometry. Result: We detected 1093 proteins in WT and 988 proteins in APP/PS1 mice at the age of six months (n=3) in synaptosomes. We identified 350 actin interacting proteins with F/G‐actin‐association in synaptosomes of WT and APP/PS1 mice. Further, 209 and 256 proteins were associated with F/G‐actin uniquely in WT and APP/PS1 mice, respectively. From synaptosomal F‐actin fractions, we detected 224 common F‐actin associated proteins in WT and APP/PS1. Along with common proteins we identified, 130 F‐actin interacting proteins are specific to WT and 70 proteins are unique to APP/PS1 mice. We identified G‐actin‐interaction only with 11 proteins in WT and 8 proteins in APP/PS1 mice in synaptosomal G‐actin fraction. Conclusion: Our result defines the synaptosomal actin interactome in mouse brain cortex from WT and APP/PS1 mice and identifies several proteins that may be critically involved in the progression of AD pathogenesis.