ArticleThe Journal of biological chemistry2012
Calretinin regulates Ca2+-dependent inactivation and facilitation of Ca(v)2.1 Ca2+ channels through a direct interaction with the α12.1 subunit.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Physiology of intracellular calcium buffering.Physiological reviews · 2023Review
- Revealing the Precise Role of Calretinin Neurons in Epilepsy: We Are on the Way.Neuroscience bulletin · 2022Review
- Parkinson mice show functional and molecular changes in the gut long before motoric disease onset.Molecular neurodegeneration · 2021Article
- NECAB1 and NECAB2 are Prevalent Calcium-Binding Proteins of CB1/CCK-Positive GABAergic Interneurons.Cerebral cortex (New York, N.Y. : 1991) · 2021Article
- GPR50 Distribution in the Mouse Cortex and Hippocampus.Neurochemical research · 2020Article
- Cytosolic CaCold Spring Harbor perspectives in biology · 2020Review
- Calretinin Functions in Malignant Mesothelioma Cells Cannot Be Replaced by the Closely Related CaInternational journal of molecular sciences · 2018Article
- Calretinin promotes invasiveness and EMT in malignant mesothelioma cells involving the activation of the FAK signaling pathway.Oncotarget · 2018Article
- Voltage-Gated Calcium Channels: Key Players in Sensory Coding in the Retina and the Inner Ear.Physiological reviews · 2018Review
- Chronic Cerebral Hypoperfusion Induced Synaptic Proteome Changes in the rat Cerebral Cortex.Molecular neurobiology · 2018Article
- The calretinin interneurons of the striatum: comparisons between rodents and primates under normal and pathological conditions.Journal of neural transmission (Vienna, Austria : 1996) · 2018Review
- NCX1 Exchanger Cooperates with Calretinin to Confer Preconditioning-Induced Tolerance Against Cerebral Ischemia in the Striatum.Molecular neurobiology · 2016Article
- Overexpression or absence of calretinin in mouse primary mesothelial cells inversely affects proliferation and cell migration.Respiratory research · 2015Article
- Routes of Ca2+ Shuttling during Ca2+ Oscillations: FOCUS ON THE ROLE OF MITOCHONDRIAL Ca2+ HANDLING AND CYTOSOLIC Ca2+ BUFFERS.The Journal of biological chemistry · 2015Article
- EF-hand protein Ca2+ buffers regulate Ca2+ influx and exocytosis in sensory hair cells.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Effect of T-type calcium channel blockers on spiral ganglion neurons of aged C57BL/6J mice.International journal of clinical and experimental medicine · 2015Article
- Ion channels under the sun.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2014Article
- Calretinin: from a "simple" Ca(2+) buffer to a multifunctional protein implicated in many biological processes.Frontiers in neuroanatomy · 2014Review
- Restricted diffusion of calretinin in cerebellar granule cell dendrites implies Ca²⁺-dependent interactions via its EF-hand 5 domain.The Journal of physiology · 2013Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Voltage-gated Ca(v)2.1 Ca(2+) channels undergo dual modulation by Ca(2+), Ca(2+)-dependent inactivation (CDI), and Ca(2+)-dependent facilitation (CDF), which can influence synaptic plasticity in the nervous system. Although the molecular determinants controlling CDI and CDF have been the focus of intense research, little is known about the factors regulating these processes in neurons. Here, we show that calretinin (CR), a Ca(2+)-binding protein highly expressed in subpopulations of neurons in the brain, inhibits CDI and enhances CDF by binding directly to α(1)2.1. Screening of a phage display library with CR as bait revealed a highly basic CR-binding domain (CRB) present in multiple copies in the cytoplasmic linker between domains II and III of α(1)2.1. In pulldown assays, CR binding to fusion proteins containing these CRBs was largely Ca(2+)-dependent. α(1)2.1 coimmunoprecipitated with CR antibodies from transfected cells and mouse cerebellum, which confirmed the existence of CR-Ca(v)2.1 complexes in vitro and in vivo. In HEK293T cells, CR significantly decreased Ca(v)2.1 CDI and increased CDF. CR binding to α(1)2.1 was required for these effects, because they were not observed upon substitution of the II-III linker of α(1)2.1 with that from the Ca(v)1.2 α(1) subunit (α(1)1.2), which lacks the CRBs. In addition, coexpression of a protein containing the CRBs blocked the modulatory action of CR, most likely by competing with CR for interactions with α(1)2.1. Our findings highlight an unexpected role for CR in directly modulating effectors such as Ca(v)2.1, which may have major consequences for Ca(2+) signaling and neuronal excitability.
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Registered trials
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.