Expression of the calcium binding proteins Necab-1,-2 and -3 in the adult mouse hippocampus and dentate gyrus

Zimmermann, Bettina; Girard, F; Mészàr, Zoltán; Celio, Marco R.

doi:10.1016/j.brainres.2013.06.004

Cited by 16 publications

(15 citation statements)

References 10 publications

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“…NECAB2 was highly expressed in the hippocampus and medial habenular nucleus, and moderately expressed in the cortex, thalamus, striatum, brainstem, and spinal cord (Fig. 11A-J), which is consistent with previous reports (Sugita et al, 2002;Zhang et al, 2016;Zimmermann et al, 2013). Double fluorescent labeling of GPR3 and NECAB2, using GPR3 knockout/LacZ knock-in mice, revealed that Ikawa et al Brain Research xxx (xxxx) xxx-xxx Fig.…”

Section: Co-expression Of Gpr3 With Necab2 In the Mouse Cnssupporting

confidence: 90%

“…Aside from the classical EF-hand Ca 2+ -binding proteins, NECAB2 is the most attractive candidate to investigate the identity of cells that express GPR3; the distribution of NECAB2 is restricted to the CA2 region in the hippocampus (Gerber et al, 2019;Girard et al, 2015;Zimmermann et al, 2013), where GPR3 is predominantly expressed (Miyagi et al, 2016). Members of the NECAB family (NECAB1-NECAB3) contain a single EF-hand domain motif at the N-terminal and a DUF176 motif at the C-terminal, and both NECAB1 and NECAB2 are primarily expressed in the brain (Sugita et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

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Detailed neuronal distribution of GPR3 and its co-expression with EF-hand calcium-binding proteins in the mouse central nervous system

et al. 2021

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The G-protein coupled receptor 3 (GPR3), a member of the class A rhodopsin-type GPR family, constitutively activates Gαs proteins without any ligands. Although there have been several reports concerning the functions of GPR3 in neurons, the physiological roles of GPR3 have not been fully elucidated. To address this issue, we analyzed GPR3 distribution in detail using fluorescence-based X-gal staining in heterozygous GPR3 knockout/LacZ knock-in mice, and further investigated the types of GPR3-expressing neurons using fluorescent double labeling with various EF-hand Ca 2+ -binding proteins. In addition to the previously reported GPR3-expressing areas, we identified GPR3 expression in the basal ganglia and in many nuclei of the cranial nerves, in regions related to olfactory, auditory, emotional, and motor functions. In addition, GPR3 was not only observed in excitatory neurons in layer V of the cerebral cortex, the CA2 region of the hippocampus, and the lateral nucleus of the thalamus, but also in γ-aminobutyric acid (GABA)-ergic interneurons in the cortex, hippocampus, thalamus, striatum, and cerebellum. GPR3 was frequently co-expressed with neuronal Ca 2+ -binding protein 2 (NECAB2) in neurons in various regions of the central nervous system, especially in the hippocampal CA2, medial habenular nucleus, lateral thalamic nucleus, dorsolateral striatum, brainstem, and spinal cord anterior horn. Furthermore, GPR3 also co-localized with NECAB2 at the tips of neurites in differentiated PC12 cells. These results suggest that GPR3 and NECAB2 are highly co-expressed in specific neurons, and that GPR3 may modulate Ca 2+ signaling by interacting with NECAB2 in specific areas of the central nervous system.

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Section: Co-expression Of Gpr3 With Necab2 In the Mouse Cnssupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Detailed neuronal distribution of GPR3 and its co-expression with EF-hand calcium-binding proteins in the mouse central nervous system

et al. 2021

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“…Necab1 mRNA was also found in the temporal lobe of human brain (Wu et al, 2007). The recent in situ hybridization (and immunohistochemistry) study in mouse shows that Necab1 mRNA + neurons are scattered the hippocampus, whereas the Necab2 mRNA is strongly expressed in pyramidal neurons of CA2 (Zimmermann et al, 2013). Single-cell RNA sequencing has shown that both Necab1 and Necab2 transcripts are existed in mouse DRG neurons.…”

Section: Candidate Ef-hand Calcium-binding Proteinsmentioning

confidence: 94%

Comparative anatomical distribution of neuronal calcium-binding protein (NECAB) 1 and -2 in rodent and human spinal cord

et al. 2016

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Neuronal calcium-binding protein 1 and -2 (NECAB1/2) localize to multiple excitatory neuron populations in the mouse spinal cord. Here, we analyzed rat and human spinal cord, combining in situ hybridization and immunohistochemistry, complementing newly collated data on mouse spinal cord for direct comparisons. Necab1/2 mRNA transcripts showed complementary distribution in rodent's spinal cord. Multiple-labeling fluorescence histochemistry with neuronal phenotypic markers localized NECAB1 to a dense fiber plexus in the dorsal horn, to neurons mainly in superficial layers and to commissural interneurons in both rodent species. NECAB1-positive (+) motor neurons were only found in mice. NECAB1 distribution in the human spinal cord was similar with the addition of NECAB1-like immunoreactivity surrounding myelinated axons. NECAB2 was mainly present in excitatory synaptic boutons in the dorsal horn of all three species, and often in calbindin-D28k(+) neuronal somata. Rodent ependymal cells expressed calbindin-D28k. In humans, they instead were NECAB2(+) and/or calretinin(+). Our results reveal that the association of NECAB2 to excitatory neuronal circuits in the spinal cord is evolutionarily conserved across the mammalian species investigated so far. In contrast, NECAB1 expression is more heterogeneous. Thus, our study suggests that the phenotypic segregation of NECAB1 and -2 to respective excitatory and inhibitory spinal systems can underpin functional modalities in determining the fidelity of synaptic neurotransmission and neuronal responsiveness, and might bear translational relevance to humans.

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“…Very recently, NECAB1/2 were shown to have complementary expression patterns in mouse hippocampus at the mRNA and protein levels, whereas NECAB3 is broadly distributed in the hippocampus (29). NECAB1-expressing cells were seen throughout the cell-sparse layers of Ammon's horn and the hilus of the dentate gyrus.…”

Section: Significancementioning

confidence: 99%

“…In contrast, NECAB2 is enriched in pyramidal cells of the CA2 region. A minority of NECAB1 + neurons were GABAergic yet did not coexpress PV, CB, or CR (29).…”

Section: Significancementioning

confidence: 99%

Neuronal calcium-binding proteins 1/2 localize to dorsal root ganglia and excitatory spinal neurons and are regulated by nerve injury

Zhang¹,

Tortoriello

Hsueh

et al. 2014

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

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Neuronal calcium (Ca 2+ )-binding proteins 1 and 2 (NECAB1/2) are members of the phylogenetically conserved EF-hand Ca 2+ -binding protein superfamily. To date, NECABs have been explored only to a limited extent and, so far, not at all at the spinal level. Here, we describe the distribution, phenotype, and nerve injury-induced regulation of NECAB1/NECAB2 in mouse dorsal root ganglia (DRGs) and spinal cord. In DRGs, NECAB1/2 are expressed in around 70% of mainly small-and medium-sized neurons. Many colocalize with calcitonin gene-related peptide and isolectin B4, and thus represent nociceptors. NECAB1/2 neurons are much more abundant in DRGs than the Ca 2+ -binding proteins (parvalbumin, calbindin, calretinin, and secretagogin) studied to date. In the spinal cord, the NECAB1/2 distribution is mainly complementary. NECAB1 labels interneurons and a plexus of processes in superficial layers of the dorsal horn, commissural neurons in the intermediate area, and motor neurons in the ventral horn. Using CLARITY, a novel, bilaterally connected neuronal system with dendrites that embrace the dorsal columns like palisades is observed. NECAB2 is present in cell bodies and presynaptic boutons across the spinal cord. In the dorsal horn, most NECAB1/2 neurons are glutamatergic. Both NECAB1/2 are transported into dorsal roots and peripheral nerves. Peripheral nerve injury reduces NECAB2, but not NECAB1, expression in DRG neurons. Our study identifies NECAB1/2 as abundant Ca 2+ -binding proteins in painrelated DRG neurons and a variety of spinal systems, providing molecular markers for known and unknown neuron populations of mechanosensory and pain circuits in the spinal cord.commissural interneurons | GAD67 | neuropathic pain | VGLUT2

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Expression of the calcium binding proteins Necab-1,-2 and -3 in the adult mouse hippocampus and dentate gyrus

Cited by 16 publications

References 10 publications

Detailed neuronal distribution of GPR3 and its co-expression with EF-hand calcium-binding proteins in the mouse central nervous system

Detailed neuronal distribution of GPR3 and its co-expression with EF-hand calcium-binding proteins in the mouse central nervous system

Comparative anatomical distribution of neuronal calcium-binding protein (NECAB) 1 and -2 in rodent and human spinal cord

Neuronal calcium-binding proteins 1/2 localize to dorsal root ganglia and excitatory spinal neurons and are regulated by nerve injury

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