ArticleMolecular psychiatry2020
Ahnak scaffolds p11/Anxa2 complex and L-type voltage-gated calcium channel and modulates depressive behavior.
Article in Molecular psychiatry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 79 citations in OpenAlex.
- Advances in calcium signalling research for the diagnosis and treatment of depression.Annals of medicine · 2026Review
- Molecular and neural circuit mechanisms of parvalbumin (PV) neurons in depression: Insights and advances.iScience · 2026Review
- Genetic alterations in SUPT6H are associated with neurodevelopmental disorders.Biochimica et biophysica acta. Molecular basis of disease · 2026Article
- Cacna1c deficiency in parvalbumin-expressing neurons promotes anxiety and passive stress-coping behavior.Scientific reports · 2026Article
- The Calcium-Binding Protein S100A10 (p11) Is Required for Normal Motor Performance by Regulating Vesicle Dynamics at Excitatory Synapses.Acta physiologica (Oxford, England) · 2026Article
- Tumor-educated platelet RNA as a diagnostic biomarker for ground-glass opacity-related lung adenocarcinoma.Translational lung cancer research · 2025Article
- ANXA2 Protein and Its Role in Neurodegeneration Processes.Life (Basel, Switzerland) · 2025Review
- A proximity proteomics pipeline with improved reproducibility and throughput.Molecular systems biology · 2024Article
- Sporadic Parathyroid Adenoma: A Pilot Study of Novel Biomarkers in Females.Medicina (Kaunas, Lithuania) · 2024Article
- Sex-specific impacts of prenatal bisphenol A exposure on genes associated with cortical development, social behaviors, and autism in the offspring's prefrontal cortex.Biology of sex differences · 2024Article
- A proximity proteomics pipeline with improved reproducibility and throughput.bioRxiv : the preprint server for biology · 2024Article
- Article
- Ahnak in the prefrontal cortex mediates behavioral correlates of stress resilience and rapid antidepressant action in mice.Frontiers in molecular neuroscience · 2024Article
- Reduction of p11 in dorsal raphe nucleus serotonergic neurons mediates depression-like behaviors.Translational psychiatry · 2023Article
- Upregulation of HDAC9 in hippocampal neurons mediates depression-like behaviours by inhibiting ANXA2 degradation.Cellular and molecular life sciences : CMLS · 2023Article
- Identification of Immune-Linked Hub Genes and Diagnostic Model Construction in Schizophrenia.Journal of molecular neuroscience : MN · 2023Article
- Involvement of brain cell phenotypes in stress-vulnerability and resilience.Frontiers in neuroscience · 2023Review
- Collagen-I influences the post-translational regulation, binding partners and role of Annexin A2 in breast cancer progression.Frontiers in oncology · 2023Article
- AHNAKs roles in physiology and malignant tumors.Frontiers in oncology · 2023Review
- Article
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Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
Abstract
Genetic polymorphisms of the L-type voltage-gated calcium channel (VGCC) are associated with psychiatric disorders including major depressive disorder. Alterations of S100A10 (p11) level are also implicated in the etiology of major depressive disorder. However, the existence of an endogenous regulator in the brain regulating p11, L-type VGCC, and depressive behavior has not been known. Here we report that Ahnak, whose function in the brain has been obscure, stabilizes p11 and Anxa2 proteins in the hippocampus and prefrontal cortex in the rodent brain. Protein levels of Ahnak, p11, and Anxa2 are highly and positively correlated in the brain. Together these data suggest the existence of an Ahnak/p11/Anxa2 protein complex. Ahnak is expressed in p11-positive as well as p11-negative neurons. Ahnak, through its N-terminal region, scaffolds the L-type pore-forming α1 subunit and, through its C-terminal region, scaffolds the β subunit of VGCC and the p11/Anxa2 complex. Cell surface expression of the α1 subunits and L-type calcium current are significantly reduced in primary cultures of Ahnak knockout (KO) neurons compared to wild-type controls. A decrease in the L-type calcium influx is observed in both glutamatergic neurons and parvalbumin (PV) GABAergic interneurons of Ahnak KO mice. Constitutive Ahnak KO mice or forebrain glutamatergic neuron-selective Ahnak KO mice display a depression-like behavioral phenotype similar to that of constitutive p11 KO mice. In contrast, PV interneuron-selective Ahnak KO mice display an antidepressant-like behavioral phenotype. Our results demonstrate L-type VGCC as an effector of the Ahnak/p11/Anxa2 complex, revealing a novel molecular connection involved in the control of depressive behavior.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.