Disease relevance of CALB1

• An intracellular target of calbindin was discovered using bacteriophage display [1].
• Our data show that, although the brain pathology is moderate to severe, there is no prominent decrease of PV, CR and CB positive neurons in the visual cortex of Alzheimer brains, but only selective changes in neuronal perikarya [2].
• Referring to a suggested neuroprotective role of CB, the results may be of relevance in the context of neuronal transplantation of patients suffering from severe Parkinson's disease [3].
• In the neonate marmoset, large numbers of putative type I ganglion cells from the apical cochlear turn transiently expressed a light and granular labeling for CB-like immunoreactivity, in addition to the cells we believe to be type II ganglion cells exhibiting a strong and solid CB-like staining [4].
• Fetal hydrocephalus causes severe alterations of CB- and PV-ir neurons in the subplate and the cortical plate: shrinkage of ir neurons, loss of process labeling and in most severe cases, entire loss of immunolabeling [5].

Psychiatry related information on CALB1

• In post-mortem brain specimens from patients dying with a clinical diagnosis of Huntington's disease (HD) immunohistochemistry showed a substantial loss from the neostriatum of neurons containing the calcium-binding protein calbindin 28K [6].
• These deficits in PV and CB are notable in also being observed in bipolar disorder, indicating how the close aetiological relationship of these two psychiatric disorders is reflected in their pathology [7].
• More significantly, interneurons that contain the calcium-binding proteins parvalbumin and calbindin are particularly resistant to degeneration in Alzheimer's disease [8].
• Compared with other markers, loss of calbindin and parvalbumin interneurons in the frontal cortex was the most significant correlate to memory deficits, suggesting a role in neurobehavioral alterations of HIV(+) METH users [9].
• In CJD, pathology was severe in pre-parasubiculum and temporal cortex, and little or absent in CA1-4; PV+ neurons were severely reduced or absent in all cases, whereas Cal+ neurons were largely preserved [10].

High impact information on CALB1

• Using immunofluorescent labeling for BrdU and for one of the neuronal markers, NeuN, calbindin or neuron specific enolase (NSE), we demonstrate that new neurons, as defined by these markers, are generated from dividing progenitor cells in the dentate gyrus of adult humans [11].
• Immunohistochemical staining showed that this nucleus is defined by a dense calbindin-positive fibre plexus in the macaque, so we applied the same staining method to sections of human thalamus [12].
• Calbindin-D28K or a related protein may serve as the mobile calcium buffer, an action similar to its function in transporting Ca2+ across intestinal epithelial cells [13].
• Thus, calbindin occurs in the primate striate cortex in a pattern almost complementary to that displaying strong cytochrome c-oxidase activity [14].
• Colocalization of neuropeptides with calbindin D28k and NADPH diaphorase in the enteric nerve plexuses of normal human ileum [15].

Chemical compound and disease context of CALB1

• We show by gain- and loss-of-function in vitro experiments that FGF-20 promotes survival and stimulates dopamine (DA) release in a calbindin-negative subset of cells that are preferentially lost in Parkinson's disease [16].
• RESULTS: Losses in n-acetylaspartate and calbindin (indicating neuronal injury and/or death) and decreases in synaptophysin immunoreactivity (indicating synaptodendritic injury) were detected along with increases in GFAP (indicating reactive gliosis) [17].
• The depletion of CB from the BFCN is likely to deprive these neurons of the capacity to buffer high levels of intracellular Ca(2+) and thus to leave them vulnerable to pathological processes, such as those in neurodegenerative disorders, which can cause increased intracellular Ca(2+), thus leading to their degeneration [18].
• In the rat brain, two weeks after intrastriatal injection of quinolinic acid (6-20 ng), surviving medium-spiny neurons in the transition zone around the lesion core exhibited a marked increase in calbindin immunoreactivity similar to that seen in Huntington's disease spiny neurons [19].
• To investigate this possibility, we compared the cellular features of calbindin immunoreactivity in grade 1-4 Huntington's disease cases with those seen in rat striatal neurons in vivo and in vitro following treatment with N-methyl-D-aspartate (NMDA) receptor agonist, quinolinic acid [19].

Biological context of CALB1

• Most importantly, the comparison of CR and Calb domain organizations questions the value of homologous modeling of EF-hand proteins, and perhaps of other protein families [20].
• Peak cell densities occurred in layer 2/upper layer 3 for CR+ neurons and in upper to midlayer 3 for CB+ cells [21].
• The sequential arrival of various afferent fiber systems in the two compartments of the striatum (patch and matrix compartment) is reflected by changing patterns of diffuse CB immunolabeling: During the second half of gestation, the patches are labeled and postnatally a changeover to matrix labeling is seen [5].
• These calbindin neurons, and the straital compartment in which they are sited, are particularly damaged in HD, suggesting that a failure of calcium buffering or homeostasis may contribute to cell death in HD [6].
• Human calbindin D(28k) is a Ca(2+) binding protein that has been implicated in the protection of cells against apoptosis [22].

Anatomical context of CALB1

• Cell bodies of interneurons immunoreactive for CB or PV were innervated only occasionally by CR multiterminal endings, whereas certain GABA neurons were surrounded by them [23].
• The patterns of staining for CalB, CalR, and GABA in the human cortex were similar to those found in monkey neocortex [24].
• Quantitative distribution of parvalbumin, calretinin, and calbindin D-28k immunoreactive neurons in the visual cortex of normal and Alzheimer cases [2].
• To verify the possible correspondence of the CB-negative territory with the cerebellar-recipient sector of the motor thalamus, we compared the distribution of cerebello-thalamic projections with the distribution of CBir in two monkeys [25].
• The substantia nigra is characterized by complementary patterns of high neuropil CB- and SMI-32-ir in pars reticulata (SNr) and high CR-ir in pars compacta (SNc) and in the ventral tegmental area (VTA) [26].

Associations of CALB1 with chemical compounds

• Myo-inositol monophosphatase is an activated target of calbindin D28k [1].
• The CB-poor shell displayed intense immunostaining for SP and CR but only weak staining for LAMP [27].
• With the use of an antibody against the calcium-binding protein, calbindin-D28K, in normal autopsy tissue and the neuronal tracers biocytin or biotinylated dextrans in in vitro slice preparations from tissue removed during surgery for intractable epilepsy, we examined the human hippocampal mossy fiber pathway [28].
• Last, oxidized calbindin D(28k) binds Ca(2+) with lower affinity than does the reduced protein [22].
• Redox sensitive cysteine residues in calbindin D28k are structurally and functionally important [22].

Physical interactions of CALB1

• Nevertheless, the calretinin-like immunostaining pattern in the teleost optic tectum was more complex than that previously described for calbindin D-28k [29].
• Calbindin D28K interacts with Ran-binding protein M: identification of interacting domains by NMR spectroscopy [30].
• The identification of the epithelial Ca(2+) channel (ECaC) complements the group of Ca(2+) transport proteins including calbindin-D28K, Na(+)/Ca(2+) exchanger and plasma membrane Ca(2+)-ATPase, which are co-expressed in 1,25(OH)2D3- responsive nephron segments [31].
• Single- and double-immunostaining procedures were used to study the distribution of the acetylcholine synthesizing enzyme choline acetyltransferase (ChAT) and the calcium binding protein calbindin D-28k in the nucleus basalis of Meynert (nbM) and in the pedunculopontine nucleus (PPN) of the squirrel monkey (Saimiri sciureus) [32].

Co-localisations of CALB1

• In addition, double immunohistochemistry revealed that cerebellar alpha-synuclein is co-localized with the neuronal marker calbindin and with glial-fibrillary acidic protein, suggesting the involvement of Purkinje cells and Bergmann glia [33].

Regulatory relationships of CALB1

• Both apo and Ca(2+)-bound calbindin was found to activate IMPase up to 250-fold, depending on the pH and substrate concentration [1].
• In the pallidum, virtually all neurons contain parvalbumin but none express calbindin [34].
• The distribution, morphology, synaptic coverage and postsynaptic targets of calbindin-containing interneurons and afferent pathways have been analyzed in the control and epileptic CA1 region of the human hippocampus [35].
• In the adult substantia nigra, calbindin-negative neurons specifically express high levels of FGFR1 (FGF receptor 1) [16].
• To provide additional evidence for the role of calcium-binding proteins in motoneuron vulnerability, VSC 4.1 cells were infected with a retrovirus carrying calbindin-D28K cDNA under the control of the promoter of the phosphoglycerate kinase gene [36].

Other interactions of CALB1

• Fluorescence spectroscopy showed that isolated calbindin and IMPase interact with an apparent equilibrium dissociation constant, K(D), of 0.9 microm [1].
• This suggests a common duplication o the calbindin/calretinin and the carbonic anhydrase ancestral genes [37].
• Neuropil labeling with parvalbumin and calbindin was most dense in layer III of the anterior cingulate cortex [38].
• In contrast, CB immunoreactivity is prevalent in medial thalamic nuclei (intralaminar and midline), the posterior complex, ventral posterior inferior nucleus, the ventral lateral anterior nucleus, ventral anterior, and ventral medial nuclei [39].
• A transient supramamillary nucleus was apparent at 14 w.g. but not after 16 w.g. As the ventromedial nucleus differentiated at 13-16 w.g., three principal parts, the ventrolateral part, the dorsomedial part, and the shell, were revealed by distribution of calbindin, calretinin, and GAP43 immunoreactivity [40].

Analytical, diagnostic and therapeutic context of CALB1

• In neither of these areas was there a significant difference between Alzheimer and control groups in the mean number of PV, CR, or CB immunoreactive neuronal profiles, counted in a cortical column going from pia to white matter [2].
• Antisera have been raised against beta-galactosidase-calretinin fusion proteins, and used to compare the distribution of calretinin with that of calbindin by two-colour immunofluorescence [41].
• ANS (8-anilinonaphthalene-1-sulfonic acid) binding and affinity chromatography on a hydrophobic column suggested that both the Ca(2+)-free and Ca(2+)-loaded form of calbindin D(28k) have exposed hydrophobic surfaces [42].
• METHODS: IMPase activity in human postmortem brain specimens with or without 10 microM human recombinant calbindin was quantified spectrophotometrically in an enzyme-linked immunosorbent assay (ELISA) reader [43].
• Confocal microscopy demonstrated that BrdU immunoreactive cells in the granule cell layer colocalized with neuron-specific markers for neuronal nuclear antigen, microtubule-associated protein-2, and calbindin D28k, indicating that the newly divided cells migrated from the subgranular zone into the granule cell layer and matured into neurons [44].

References