Roles and functions of Atp6ap2 in the brain

Bracke, Alexander; Halbach, Oliver von Bohlen und

doi:10.4103/1673-5374.241428

Cited by 8 publications

(3 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These data are consistent with a number of other crucial V-ATPase modulators—such as the accessory protein ATP6AP2—that does not affect subunit expression, but does disturb the ratio of membrane-assembled ATP6V1B2 to V0 subunits [ 55 , 56 ]. Of note, de novo ATP6AP2 deletion variants have also been described in neurological disease, altering neuronal development, LC3b abundance and lysosomal function when modelled in the mouse and human stem cell-derived neurons [ 56 , 57 ]. Furthermore, absence of VPS50, another V-ATPase accessory protein, not only alters dense-core vesicle acidification, but is also implicated in neural tube formation in humans [ 58 ].…”

Section: Discussionmentioning

confidence: 99%

The Ncoa7 locus regulates V-ATPase formation and function, neurodevelopment and behaviour

Castroflorio

Hoed

Svistunova

et al. 2020

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

Members of the Tre2/Bub2/Cdc16 (TBC), lysin motif (LysM), domain catalytic (TLDc) protein family are associated with multiple neurodevelopmental disorders, although their exact roles in disease remain unclear. For example, nuclear receptor coactivator 7 (NCOA7) has been associated with autism, although almost nothing is known regarding the mode-of-action of this TLDc protein in the nervous system. Here we investigated the molecular function of NCOA7 in neurons and generated a novel mouse model to determine the consequences of deleting this locus in vivo. We show that NCOA7 interacts with the cytoplasmic domain of the vacuolar (V)-ATPase in the brain and demonstrate that this protein is required for normal assembly and activity of this critical proton pump. Neurons lacking Ncoa7 exhibit altered development alongside defective lysosomal formation and function; accordingly, Ncoa7 deletion animals exhibited abnormal neuronal patterning defects and a reduced expression of lysosomal markers. Furthermore, behavioural assessment revealed anxiety and social defects in mice lacking Ncoa7. In summary, we demonstrate that NCOA7 is an important V-ATPase regulatory protein in the brain, modulating lysosomal function, neuronal connectivity and behaviour; thus our study reveals a molecular mechanism controlling endolysosomal homeostasis that is essential for neurodevelopment. Graphic abstract

show abstract

Section: Discussionmentioning

confidence: 99%

The Ncoa7 locus regulates V-ATPase formation and function, neurodevelopment and behaviour

Castroflorio

Hoed

Svistunova

et al. 2020

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

show abstract

“…Thus, local expression of ATP6AP2 may be a key enzyme for neurodegenerative diseases linking intracellular trafficking with disease progression, i.e., post-COVID-19. ATP6AP2 in neurons is required for the loading of neurotransmitters into synaptic vesicles by providing energy from proton-pumping V-ATPases [60]. The ATP6AP2 membrane protein complexes possess numerous subunit isoforms that are involved in both (Wingless-related integration site) Wnt signaling and the RAS that regulates blood pressure.…”

Section: Discussionmentioning

confidence: 99%

Targeting the High-Density Lipoprotein Proteome for the Treatment of Post-Acute Sequelae of SARS-CoV-2

Grote,

Schaefer,

Soufi

et al. 2024

IJMS

View full text Add to dashboard Cite

Here, we target the high-density lipoprotein (HDL) proteome in a case series of 16 patients with post-COVID-19 symptoms treated with HMG-Co-A reductase inhibitors (statin) plus angiotensin II type 1 receptor blockers (ARBs) for 6 weeks. Patients suffering from persistent symptoms (post-acute sequelae) after serologically confirmed SARS-CoV-2 infection (post-COVID-19 syndrome, PCS, n = 8) or following SARS-CoV-2 vaccination (PVS, n = 8) were included. Asymptomatic subjects with corresponding serological findings served as healthy controls (n = 8/8). HDL was isolated using dextran sulfate precipitation and the HDL proteome of all study participants was analyzed quantitatively by mass spectrometry. Clinical symptoms were assessed using questionnaires before and after therapy. The inflammatory potential of the patients’ HDL proteome was addressed in human endothelial cells. The HDL proteome of patients with PCS and PVS showed no significant differences; however, compared to controls, the HDL from PVS/PCS patients displayed significant alterations involving hemoglobin, cytoskeletal proteins (MYL6, TLN1, PARVB, TPM4, FLNA), and amyloid precursor protein. Gene Ontology Biological Process (GOBP) enrichment analysis identified hemostasis, peptidase, and lipoprotein regulation pathways to be involved. Treatment of PVS/PCS patients with statins plus ARBs improved the patients’ clinical symptoms. After therapy, three proteins were significantly increased (FAM3C, AT6AP2, ADAM10; FDR < 0.05) in the HDL proteome from patients with PVS/PCS. Exposure of human endothelial cells with the HDL proteome from treated PVS/PCS patients revealed reduced inflammatory cytokine and adhesion molecule expression. Thus, HDL proteome analysis from PVS/PCS patients enables a deeper insight into the underlying disease mechanisms, pointing to significant involvement in metabolic and signaling disturbances. Treatment with statins plus ARBs improved clinical symptoms and reduced the inflammatory potential of the HDL proteome. These observations may guide future therapeutic strategies for PVS/PCS patients.

show abstract

“…PRR is highly expressed in neurons and some microglia cells and has been detected in several brain regions implicated in cardiovascular and autonomic control including the subfornical organ (SFO), paraventricular nucleus (PVN), nucleus of the solitary tract (NTS), and the rostral ventrolateral medulla (RVLM) [63•, 64]. Despite initial reports indicating that PRR might be involved in hypertension through local generation of ANG-II, other roles that are independent of RAS activation have been described (reviewed in [65]). For instance, the transmembrane domain of the PRR interacts with the vacuolar H(+)-ATPase and plays an important role in lysosomal function and neuronal development [66].…”

Section: Activation Of Renin By Prorenin Receptormentioning

confidence: 99%

The Renin-Angiotensin System in the Central Nervous System and Its Role in Blood Pressure Regulation

et al. 2020

View full text Add to dashboard Cite

Purpose of the Review The main goal of this article is to discuss how the development of state-of-the-art technology has made it possible to address fundamental questions related to how the renin-angiotensin system (RAS) operates within the brain from the neurophysiological and molecular perspective. Recent Findings The existence of the brain RAS remains surprisingly controversial. New sensitive in situ hybridization techniques and novel transgenic animals expressing reporter genes have provided pivotal information of the expression of RAS genes within the brain. We discuss studies using genetically engineered animals combined with targeted viral microinjections to study molecular mechanisms implicated in the regulation of the brain RAS. We also discuss novel drugs targeting the brain RAS that have shown promising results in clinical studies and trials. Summary Over the last 50 years, several new physiological roles of the brain RAS have been identified. In the coming years, efforts to incorporate cutting-edge technologies such as optogenetics, chemogenetics, and single-cell RNA sequencing will lead to dramatic advances in our full understanding of how the brain RAS operates at molecular and neurophysiological levels. Keywords Renin. Prorenin receptor. Angiotensin receptor. Biased agonist. Blood pressure. Neurophysiology This article is part of the Topical Collection on Inflammation and Cardiovascular Diseases

show abstract

Roles and functions of Atp6ap2 in the brain

Cited by 8 publications

References 60 publications

The Ncoa7 locus regulates V-ATPase formation and function, neurodevelopment and behaviour

The Ncoa7 locus regulates V-ATPase formation and function, neurodevelopment and behaviour

Targeting the High-Density Lipoprotein Proteome for the Treatment of Post-Acute Sequelae of SARS-CoV-2

The Renin-Angiotensin System in the Central Nervous System and Its Role in Blood Pressure Regulation

Contact Info

Product

Resources

About