EFhd2 brain interactome reveals its association with different cellular and molecular processes

Abstract

EFhd2 is a conserved calcium‐binding protein that is highly expressed in the central nervous system. We have shown that EFhd2 interacts with tau protein, a key pathological hallmark in Alzheimer's disease and related dementias. However, EFhd2’s physiological and pathological functions in the brain are still poorly understood. To gain insights into its physiological function, we identified proteins that co‐immunoprecipitated with EFhd2 from mouse forebrain and hindbrain, using tandem mass spectrometry (MS). In addition, quantitative mass spectrometry was used to detect protein abundance changes due to the deletion of the Efhd2 gene in mouse forebrain and hindbrain regions. Our data show that mouse EFhd2 is associated with cytoskeleton components, vesicle trafficking modulators, cellular stress response‐regulating proteins, and metabolic proteins. Moreover, proteins associated with the cytoskeleton, vesicular transport, calcium signaling, stress response, and metabolic pathways showed differential abundance in Efhd2(−/−) mice. This study presents, for the first time, an EFhd2 brain interactome that it is associated with different cellular and molecular processes. These findings will help prioritize further studies to investigate the mechanisms by which EFhd2 modulates these processes in physiological and pathological conditions of the nervous system.

Exploring Promising Biomarkers for Alzheimer’s Disease through the Computational Analysis of Peripheral Blood Single-Cell RNA Sequencing Data

“…Mielenz and Gunn-Moore found that the down-regulation of the protein could enhance synaptic delivery through kinesin-mediated transport and regulate synaptic plasticity through F-actin binding and Cdc42, Rac and Rho activity [28]. Previous studies identified how EFhd2 interacts with pathologically aggregated tau protein and accomplishes the formation of an amyloid structure [29], while recently, it was reported that EFhd2 in mice interact with several intracellular components such as vesicle trafficking modulators, cellular stress response-regulating proteins, and metabolic proteins [30]. Pathway enrichment analysis showed that a EFhd2 was enriched in the RHO GTPase cycle and signaling by Rho GTases and Miro GTPases (Table S5), which are involved in the regulation of cell migration, neuronal development and mitochondrial distribution with neuronal activity [31,32].…”

Sertoli cell-enriched proteins in mouse and human testicular interstitial fluid

“…Immunohistochemical analyses revealed that EFHD2 protein was detected in mouse Sertoli cell nuclei whereas MARCKSL1 and SDC4 were detected in Sertoli cell cytoplasm and nuclei. According to data from the Human Protein Atlas, EFHD2 protein is localized to human Sertoli cell nuclei and perinuclear cytoplasm [16] and is expressed in a range of cell types in the body, where it can regulate calcium signalling, vesicle transport, signal transduction and cellular stress responses [37]. MARCKSL1 is also localized in human…”