Distribution of a specific calcium‐binding protein of the S100 protein family, S100A6 (calcyclin), in subpopulations of neurons and glial cells of the adult rat nervous system

Yamashita, Norifumi; Ilg, Evelyn C.; Schäfer, Beat W.; Heizmann, Claus W.; Kosaka, Toshio

doi:10.1002/(sici)1096-9861(19990208)404:2<235::aid-cne8>3.3.co;2-z

Cited by 11 publications

(14 citation statements)

References 33 publications

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“…Initially, it was thought to possess a hydrophobic N-terminal extension of 18 residues, but we demonstrate here that S100A5 isolated from rat brain does not contain this tail. Furthermore, we describe 1 the cation binding properties of the recombinant short form of human S100A5 and investigate the distribution of S100A5 in rat brain by immunohistochemistry with a specific antiserum, comparing it to that of S100A6, which is expressed in a large subset of neurons, glial cells, and sensory afferent fibers in brain (21).…”

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confidence: 63%

“…They were incubated overnight in a mixture of human recombinant S100A5 rabbit antiserum (1:2000) and human recombinant S100A6 goat antiserum (1:5000; see Ref. 21) diluted in Tris buffer, pH 7.4, containing 2% normal donkey serum and 0.2% Triton. Sections were then washed, incubated for 30 min at room temperature with the corresponding secondary antibodies coupled to Cy2 and Cy3 (Jackson Immunoresearch, West Grove, PA), washed again, and coverslipped with buffered glycerol.…”

Section: Methodsmentioning

confidence: 99%

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Brain S100A5 Is a Novel Calcium-, Zinc-, and Copper Ion-binding Protein of the EF-hand Superfamily

Schäfer

Fritschy

Murmann

et al. 2000

Journal of Biological Chemistry

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S100A5 is a novel member of the EF-hand superfamily of calcium-binding proteins that is poorly characterized at the protein level. Immunohistochemical analysis demonstrates that it is expressed in very restricted regions of the adult brain. Here we characterized the human recombinant S100A5, especially its interaction with Ca 2؉ , Zn 2؉ , and Cu 2؉. Flow dialysis revealed that the homodimeric S100A5 binds four Ca 2؉ ions with strong positive cooperativity and an affinity 20 -100-fold higher than the other S100 proteins studied under identical conditions. S100A5 also binds two Zn 2؉ ions and four Cu 2؉ ions per dimer. Cu 2؉ binding strongly impairs the binding of Ca 2؉ ; however, none of these ions change the ␣-helical-rich secondary structure. After covalent labeling of an exposed thiol with 2-(4-(iodoacetamide)anilino)-naphthalene-6-sulfonic acid, binding of Cu 2؉ , but not of Ca 2؉ or Zn 2؉ , strongly decreased its fluorescence. In light of the three-dimensional structure of S100 proteins, our data suggest that in each subunit the single Zn 2؉ site is located at the opposite side of the EF-hands. The two Cu 2؉ -binding sites likely share ligands of the EF-hands. The potential role of S100A5 in copper homeostasis is discussed.Calcium, a versatile second messenger of extracellular signals inside the cell, binds to a multitude of cytosolic Ca 2ϩ -binding proteins each of which can, in turn, regulate several effector proteins. The S100 protein family (18 different members) constitutes the largest group of Ca 2ϩ -binding proteins of the EF-hand type (1, 2). At least 13 S100 genes are clustered on human chromosome 1q21, leading to the designation S100A1 to S100A13 for the protein products of these genes (3). Their expression is cell-and tissue-specific, and different human diseases have been associated with deregulated expression (4, 5). S100 proteins are non-covalent homodimers with the notable exception of the heterodimeric S100A8-S100A9. Each monomer possesses 2 EF-hands as follows: a classical C-terminal EFhand with a canonical Ca 2ϩ -binding loop of 12 amino acids and a N-terminal EF-hand with a loop of 14 amino acids which is specific for S100 proteins. This structural difference likely is the reason for the large difference in the Ca 2ϩ affinities of the N-and C-terminal EF-hands. The affinities of S100 proteins for Ca 2ϩ are in general rather low with [Ca 2ϩ ] 0.5 1 values of 100 -300 mM (for review see Refs. 2 and 6), and in 6 out of 8 studied cases binding of Ca 2ϩ displays positive cooperativity. Zn 2ϩ binds to several S100 proteins; the Zn 2ϩ and Ca 2ϩ sites are distinct and can modify the affinity for Ca 2ϩ . S100B binds four Zn 2ϩ ions with concomitant 10-fold increases of the Ca 2ϩ affinity (7). High affinity binding of two Zn 2ϩ to the S100A12 dimer leads to induction of two high affinity Ca 2ϩ -binding sites (8). S100A3 binds eight Zn 2ϩ , but without effect on the affinity for Ca 2ϩ (9, 10). S100A2 binds four Zn 2ϩ with high affinity, in a manner antagonistic to Ca 2ϩ (11). Recently it was reported...

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confidence: 63%

Section: Methodsmentioning

confidence: 99%

Brain S100A5 Is a Novel Calcium-, Zinc-, and Copper Ion-binding Protein of the EF-hand Superfamily

Schäfer

Fritschy

Murmann

et al. 2000

Journal of Biological Chemistry

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“…The localization of S100A6 has been also studied in transformed (15,29) or normal tissues (20,30), and in cultured smooth muscle cells (31) using a polyclonal antibody. In this study we have reinvestigated the Ca 2ϩ -dependent subcellular localization of S100A6 using a novel highly specific monoclonal antibody and show that the protein localizes to the plasma * This work was supported by the Austrian Science Foundation (P-11845).…”

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confidence: 64%

Ca2+-dependent Association of S100A6 (Calcyclin) with the Plasma Membrane and the Nuclear Envelope

Stradal

Gimona

1999

Journal of Biological Chemistry

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Expression of S100A6 (Calcyclin), a member of the S100 family and of Zn 2؉ -binding proteins is elevated in a number of malignant tumors. In vitro the protein associates with several actin-binding proteins and annexins in a Ca 2؉ -dependent manner. We have now studied the subcellular localization of S100A6 using a new, specific monoclonal antibody. Immunofluorescence microscopy of unfixed, ultrathin, frozen sections demonstrated a dual localization of S100A6 at the nuclear envelope and the plasma membrane of porcine smooth muscle only in the presence of Ca 2؉ . The same localization was found by immunofluorescence and immunogold electron microscopy as well as by confocal laser scanning microscopy with cultured, fixed, human CaKi-2 and porcine ST interphase cells. Upon cell division, however, S100A6 was found exclusively in the cytoplasm. Cell fractionation studies showed that S100A6 was present in the microsomal fraction in the presence of Ca 2؉ and was released from this fraction by the addition of EGTA/ EDTA but not by Triton X-100. The data demonstrate that S100A6 is localized both at the plasma membrane and the nuclear envelope in vivo and suggest a Ca 2؉ -dependent interaction with annexins or other components of the nuclear envelope.

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“…However, mice completely lacking S100B developed normally and there was no detectable abnormality in histological architecture of the mutant brain. There are two other S100 family proteins, S100A1 and S100A6 (33,34), that are expressed in rodent glial cells albeit at much lower levels than S100B. We found no compensatory expression of S100A1 and S100A6 mRNA in the mutant brain (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Glial protein S100B modulates long-term neuronal synaptic plasticity

Nishiyama

Knöpfel

Endo

et al. 2002

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

246

168

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Glial cells are traditionally regarded as elements for structural support and ionic homeostasis, but have recently attracted attention as putative integral elements of the machinery involved in synaptic transmission and plasticity. Here, we demonstrate that calcium-binding protein S100B, which is synthesized in considerable amounts in astrocytes (a major glial cell subtype), modulates long-term synaptic plasticity. Mutant mice devoid of S100B developed normally and had no detectable abnormalities in the cytoarchitecture of the brain. These mutant mice, however, had strengthened synaptic plasticity as identified by enhanced longterm potentiation (LTP) in the hippocampal CA1 region. Perfusion of hippocampal slices with recombinant S100B proteins reversed the levels of LTP in the mutant slices to those of the wild-type slices, indicating that S100B might act extracellularly. In addition to enhanced LTP, mutant mice had enhanced spatial memory in the Morris water maze test and enhanced fear memory in the contextual fear conditioning. The results indicate that S100B is a glial modulator of neuronal synaptic plasticity and strengthen the notion that glial-neuronal interaction is important for information processing in the brain.S everal lines of evidence suggest that glial cells play an active role in excitatory neurotransmission in the central nervous system (1, 2). For instance, astrocytes can release glutamate in response to physiological increases in their intracellular calcium concentration, and then evoke substantial glutamatergic currents in neighboring neurons (3). Oligodendrocyte precursor cells directly receive glutamatergic inputs from hippocampal pyramidal neurons (4). These findings, together with earlier studies showing that glial cells express many types of neurotransmitter receptors and respond to neurotransmitter by generating slowly propagating calcium waves (5), suggest that glialneuronal reciprocal signaling may play a role in synaptic plasticity and eventually in information processing in the brain. Indeed, this notion has been supported by the findings that the mice devoid of glial fibrillary acidic protein (GFAP: an intermediate filament specific to astrocytes) showed enhanced longterm potentiation (LTP) in the hippocampal CA1 region and decreased long-term depression in the cerebellum associated with impaired eye-blink conditioning (6, 7). However, the molecular mechanism underlying glial-neuronal interactions is poorly understood.One of the candidates that might be involved in glia-to-neuron signaling is the calcium-binding protein S100B. S100B is a member of the S100 family of proteins containing two EF-handtype calcium-binding domains (8). The highest level of expression of the S100B protein is in the brain and is found primarily in the cytoplasm of astrocytes (9). Results of in vitro studies suggest a variety of intracellular functions of S100B, including cell growth, cell structure, energy metabolism, and calcium homeostasis (8). S100B is secreted from astrocytes, suggesting that it might ...

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Distribution of a specific calcium‐binding protein of the S100 protein family, S100A6 (calcyclin), in subpopulations of neurons and glial cells of the adult rat nervous system

Cited by 11 publications

References 33 publications

Brain S100A5 Is a Novel Calcium-, Zinc-, and Copper Ion-binding Protein of the EF-hand Superfamily

Brain S100A5 Is a Novel Calcium-, Zinc-, and Copper Ion-binding Protein of the EF-hand Superfamily

Ca2+-dependent Association of S100A6 (Calcyclin) with the Plasma Membrane and the Nuclear Envelope

Glial protein S100B modulates long-term neuronal synaptic plasticity

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