Altered Postsynaptic-Density-Levels of Caldendrin in the Para-Chloroamphetamine-Induced Serotonin Syndrome but not in the Rat Ketamine Model of Psychosis

Sahin, Jale; Putzke, Jörg; Tischmeyer, Wolfgang; Gundelfinger, Eckart D.; Kreutz, Michael R.

doi:10.1007/s11064-009-9925-8

Cited by 3 publications

(2 citation statements)

References 23 publications

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“…The number of caldendrin-positive neurons is reduced in the prefrontal cortex of postmortem brains from chronic schizophrenics (Bernstein et al, 2007) and caldendrin levels at the postsynaptic density are reduced in a rat model of psychosis (Smalla et al, 2009). In addition, variations in the gene encoding Ca v 1.2, CACNA1C , are strongly associated with major depression, autism spectrum, schizophrenia, bipolar disorder, and attention deficit hyperactivity disorder (Cross-Disorder Group of the Psychiatric Genomics and Genetic Risk Outcome of Psychosis, 2013).…”

Section: Discussionmentioning

confidence: 99%

Localization and expression of CaBP1/caldendrin in the mouse brain

et al. 2014

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Ca2+ binding protein 1 (CaBP1) and caldendrin are alternatively spliced variants of a subfamily of Ca2+ binding proteins with high homology to calmodulin. Although CaBP1 and caldendrin regulate effectors including plasma membrane and intracellular Ca2+ channels in heterologous expression systems, little is known about their functions in vivo. Therefore, we generated mice deficient in CaBP1/ caldendrin expression (C-KO) and analyzed the expression and cellular localization of CaBP1 and caldendrin in the mouse brain. Immunoperoxidase labeling with antibodies recognizing both CaBP1 and caldendrin was absent in the brain of C-KO mice, but was intense in multiple brain regions of wild-type mice. By western blot, the antibodies detected two proteins that were absent in the C-KO mouse and consistent in size with caldendrin variants originating from alternative translation initiation sites. By quantitative PCR, caldendrin transcript levels were far greater than those for CaBP1 particularly in the cerebral cortex and hippocampus. In the frontal cortex but not in the hippocampus, caldendrin expression increased steadily from birth. By double-label immunofluorescence, CaBP1/caldendrin was localized in principal neurons and parvalbumin-positive interneurons. In the cerebellum, CaBP1/caldendrin antibodies labeled interneurons in the molecular layer and in basket cell terminals surrounding the soma and axon initial segment of Purkinje neurons, but immunolabeling was absent in Purkinje neurons. We conclude that CaBP1/ caldendrin is localized both pre- and postsynaptically where it may regulate Ca2+ signaling and excitability in select groups of excitatory and inhibitory neurons.

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Section: Discussionmentioning

confidence: 99%

Localization and expression of CaBP1/caldendrin in the mouse brain

et al. 2014

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“…Interestingly, caldendrin protein levels are also regulated in human schizophrenia (Bernstein et al, 2007) and in mouse models of drug-induced psychosis (Smalla et al, 2009). Fewer caldendrin-immunopositive neurons are found in the left dorsolateral prefrontal cortex in schizophrenia patients, and it is tempting to speculate that synaptic and/or dendritic Ca 2+ -signaling is altered in schizophrenia due to a redistribution of the protein.…”

Section: On a Putative Role Of Calneuron-1 And Caldendrin In Mental Dmentioning

confidence: 99%

Caldendrin and Calneurons—EF-Hand CaM-Like Calcium Sensors With Unique Features and Specialized Neuronal Functions

Mundhenk

Fusi

Kreutz

2019

Front. Mol. Neurosci.

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The calmodulin (CaM)-like Ca2+-sensor proteins caldendrin, calneuron-1 and -2 are members of the neuronal calcium-binding protein (nCaBP)-family, a family that evolved relatively late during vertebrate evolution. All three proteins are abundant in brain but show a strikingly different subcellular localization. Whereas caldendrin is enriched in the postsynaptic density (PSD), calneuron-1 and -2 accumulate at the trans-Golgi-network (TGN). Caldendrin exhibit a unique bipartite structure with a basic and proline-rich N-terminus while calneurons are the only EF-Hand CaM-like transmembrane proteins. These uncommon structural features come along with highly specialized functions of calneurons in Golgi-to-plasma-membrane trafficking and for caldendrin in actin-remodeling in dendritic spine synapses. In this review article, we will provide a synthesis of available data on the structure and biophysical properties of all three proteins. We will then discuss their cellular function with special emphasis on synaptic neurotransmission. Finally, we will summarize the evidence for a role of these proteins in neuropsychiatric disorders.

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Molecular Dynamics of the Neuronal EF-Hand Ca2+-Sensor Caldendrin

et al. 2014

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Caldendrin, L- and S-CaBP1 are CaM-like Ca2+-sensors with different N-termini that arise from alternative splicing of the Caldendrin/CaBP1 gene and that appear to play an important role in neuronal Ca2+-signaling. In this paper we show that Caldendrin is abundantly present in brain while the shorter splice isoforms L- and S-CaBP1 are not detectable at the protein level. Caldendrin binds both Ca2+ and Mg2+ with a global Kd in the low µM range. Interestingly, the Mg2+-binding affinity is clearly higher than in S-CaBP1, suggesting that the extended N-terminus might influence Mg2+-binding of the first EF-hand. Further evidence for intra- and intermolecular interactions of Caldendrin came from gel-filtration, surface plasmon resonance, dynamic light scattering and FRET assays. Surprisingly, Caldendrin exhibits very little change in surface hydrophobicity and secondary as well as tertiary structure upon Ca2+-binding to Mg2+-saturated protein. Complex inter- and intramolecular interactions that are regulated by Ca2+-binding, high Mg2+- and low Ca2+-binding affinity, a rigid first EF-hand domain and little conformational change upon titration with Ca2+ of Mg2+-liganted protein suggest different modes of binding to target interactions as compared to classical neuronal Ca2+-sensors.

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Altered Postsynaptic-Density-Levels of Caldendrin in the Para-Chloroamphetamine-Induced Serotonin Syndrome but not in the Rat Ketamine Model of Psychosis

Cited by 3 publications

References 23 publications

Localization and expression of CaBP1/caldendrin in the mouse brain

Localization and expression of CaBP1/caldendrin in the mouse brain

Caldendrin and Calneurons—EF-Hand CaM-Like Calcium Sensors With Unique Features and Specialized Neuronal Functions

Molecular Dynamics of the Neuronal EF-Hand Ca2+-Sensor Caldendrin

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