Calretinin Regulates Ca2+-dependent Inactivation and Facilitation of Cav2.1 Ca2+ Channels through a Direct Interaction with the α12.1 Subunit

Christel, Carl J.; Schaer, Raphael; Wang, Shiyi; Henzi, Thomas; Kreiner, Lisa; Grabs, Detlev; Schwaller, Beat; Lee, Amy

doi:10.1074/jbc.m112.406363

Cited by 27 publications

(24 citation statements)

References 57 publications

(32 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In line, WiDr cells subjected to differentiation by glucose starvation or treatment by butyrate were shown to downregulate CR expression . Although it is generally assumed that CR's functions are directly linked to its well‐characterized function as a Ca 2+ buffer, it has also been hypothesized that CR might have additional functions as a Ca 2+ sensor, and first evidence was provided showing an interaction of CR with Ca V 2.1 in neurons affecting the function of this Ca 2+ channel . Whether CR has also binding partners in other cell types ( e.g ., MM cells) remains to be investigated.…”

Section: Discussionmentioning

confidence: 99%

“…The median survival time of patients diagnosed with MM is rarely over 1 year, and therefore, identifying new targets for therapy is of high importance . Calretinin (CR), the gene product from CALB2 , is a 30‐kDa calcium‐binding protein of the EF‐hand family and is mostly considered as a cytosolic Ca 2+ ‐buffering protein, but has additional functions as a Ca 2+ sensor as evidenced by the direct interaction of CR with the voltage‐gated Ca 2+ channel Ca V 2.1 in neurons . CR is expressed in a subpopulation of neurons in the central and peripheral nervous system, as well as in specialized cells including Leydig cells …”

mentioning

confidence: 99%

See 1 more Smart Citation

Calretinin is essential for mesothelioma cell growth/survival in vitro: A potential new target for malignant mesothelioma therapy?

Blum

Schwaller

2013

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

Malignant mesothelioma (MM) are highly aggressive asbestos-related neoplasms, which show strong chemotherapy resistance, and there is no effective cure for MM so far. Calretinin (CR) is widely used as a diagnostic marker for epithelioid and mixed (biphasic) mesothelioma; however, little is known about CR's putative functions in tumorigenesis. CR protects against asbestos-induced acute cytotoxicity mediated by the AKT/PI3K pathway, and furthermore, SV40 early region genes are able to upregulate CR in mesothelial cells. However, the precise role of CR in mesothelioma is still unknown. Downregulation of CR via lentiviral-mediated short-hairpin RNA significantly decreased the viability and proliferation of mesothelioma cells in vitro.The effect was strong in epithelioid-dominated cell lines (ZL55 and MSTO-211H). A weaker and delayed effect was observed in mesothelioma cells with prevalent sarcomatoid morphology (SPC111, SPC212 and ZL34). The specificity of the effect was confirmed by stable enhanced green fluorescent protein-CR expression in mesothelioma cell lines and subsequent downregulation. Depletion of CR led these cancer cell lines to enter apoptosis within 72 hr postinfection via strong activation of the intrinsic caspase 9-dependent pathway. Downregulation of CR in immortalized mesothelial cells LP9/TERT-1 strongly blocked proliferation and caused a G 1 block without decreasing viability or activating apoptosis pathways. These results demonstrate that downregulation of CR had a strong effect on the viability of MM cells and that CR is essential for cells derived from MM. The authors anticipate these findings to reveal CR as a highly interesting new putative therapeutic target for mesothelioma treatment of especially the epithelioid, as well as of the mixed and sarcomatoid type.Malignant mesothelioma (MM) is a neoplasm developing from mesothelial cells of the pleural, pericardial and peritoneal cavities and is prevalently associated with asbestos exposure. In the United States alone, more than 20 million people were exposed to asbestos and could potentially develop MM.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Calretinin is essential for mesothelioma cell growth/survival in vitro: A potential new target for malignant mesothelioma therapy?

Blum

Schwaller

2013

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

show abstract

“…Alternatively, EF-hand Ca 2+ -binding proteins might directly interact with the channel, which is established for calmodulin and CaBPs (52)(53)(54)(55). Indeed, CR suppresses CDI in Ca V 2.1 channels (but not Ca V 1.2 channels) in HEK 293-T cells (56).…”

Section: +mentioning

confidence: 99%

EF-hand protein Ca ²⁺ buffers regulate Ca ²⁺ influx and exocytosis in sensory hair cells

Pangršič

Gabrielaitis

Michanski

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

100

142

View full text Add to dashboard Cite

EF-hand Ca2+-binding proteins are thought to shape the spatiotemporal properties of cellular Ca2+ signaling and are prominently expressed in sensory hair cells in the ear. Here, we combined genetic disruption of parvalbumin-α, calbindin-D28k, and calretinin in mice with patch-clamp recording, in vivo physiology, and mathematical modeling to study their role in Ca2+ signaling, exocytosis, and sound encoding at the synapses of inner hair cells (IHCs). IHCs lacking all three proteins showed excessive exocytosis during prolonged depolarizations, despite enhanced Ca2+-dependent inactivation of their Ca2+ current. Exocytosis of readily releasable vesicles remained unchanged, in accordance with the estimated tight spatial coupling of Ca2+ channels and release sites (effective “coupling distance” of 17 nm). Substitution experiments with synthetic Ca2+ chelators indicated the presence of endogenous Ca2+ buffers equivalent to 1 mM synthetic Ca2+-binding sites, approximately half of them with kinetics as fast as 1,2-Bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA). Synaptic sound encoding was largely unaltered, suggesting that excess exocytosis occurs extrasynaptically. We conclude that EF-hand Ca2+ buffers regulate presynaptic IHC function for metabolically efficient sound coding.

show abstract

“…In the present study, we identified (with at least 3 peptides) 23 proteins with significantly increased (Table 1) and 23 proteins with decreased ( Table 2) (1) - (Chihara et al, 2007), (2) - (Folci et al, 2014), (3) - (Chen et al, 2002), (4) - (Tanaka et al, 2000), (5) - (Ding and Shen, 2008), (6) - (Na et al, 2012), (7) - (Lyon et al, 2007), (8) - (Sweatt et al, 2004), (9) - (Bahn et al, 2002), (10) - (Manya et al, 1998), (11) - (Kamada et al, 2003), (12) - (McKenna et al, 2000), (13) - (Christel et al, 2012), (GO) -According to Gene Ontology database. …”

Section: Functional Clusters Of Altered Proteinsmentioning

confidence: 99%

Chronic Cerebral Hypoperfusion Induced Synaptic Proteome Changes in the rat Cerebral Cortex

et al. 2017

View full text Add to dashboard Cite

Chronic cerebral hypoperfusion (CCH) evokes mild cognitive impairment (MCI) and contributes to the progression of vascular dementia and Alzheimer's disease (AD). How CCH 2 induces these neurodegenerative processes that may spread along the synaptic network and whether they are detectable at the synaptic proteome level of the cerebral cortex remains to be established.In the present study, we report the synaptic protein changes in the cerebral cortex after stepwise bilateral common carotid artery occlusion (BCCAO) induced CCH in the rat. The occlusions were confirmed with Magnetic Resonance Angiography 5 weeks after the surgery.Synaptosome fractions were prepared using sucrose gradient centrifugation from cerebral cortex dissected 7 weeks after the occlusion. The synaptic protein differences between the sham operated and CCH groups were analysed with label free nanoUHPLC-MS/MS.

show abstract

Calretinin Regulates Ca2+-dependent Inactivation and Facilitation of Cav2.1 Ca2+ Channels through a Direct Interaction with the α12.1 Subunit

Cited by 27 publications

References 57 publications

Calretinin is essential for mesothelioma cell growth/survival in vitro: A potential new target for malignant mesothelioma therapy?

Calretinin is essential for mesothelioma cell growth/survival in vitro: A potential new target for malignant mesothelioma therapy?

EF-hand protein Ca ²⁺ buffers regulate Ca ²⁺ influx and exocytosis in sensory hair cells

Chronic Cerebral Hypoperfusion Induced Synaptic Proteome Changes in the rat Cerebral Cortex

Contact Info

Product

Resources

About

Calretinin Regulates Ca2+-dependent Inactivation and Facilitation of Cav2.1 Ca2+ Channels through a Direct Interaction with the α12.1 Subunit

Cited by 27 publications

References 57 publications

Calretinin is essential for mesothelioma cell growth/survival in vitro: A potential new target for malignant mesothelioma therapy?

Calretinin is essential for mesothelioma cell growth/survival in vitro: A potential new target for malignant mesothelioma therapy?

EF-hand protein Ca 2+ buffers regulate Ca 2+ influx and exocytosis in sensory hair cells

Chronic Cerebral Hypoperfusion Induced Synaptic Proteome Changes in the rat Cerebral Cortex

Contact Info

Product

Resources

About

EF-hand protein Ca ²⁺ buffers regulate Ca ²⁺ influx and exocytosis in sensory hair cells