Ryanodine and inositol trisphosphate receptors coexist in avian cerebellar Purkinje neurons.

Walton, Philip D.; Airey, Judith A.; Sutko, John L.; Beck, Claudia F.; Mignery, Gregory A.; Sudhof, T. C.; Deerinck, Thomas J.; Ellisman, Mark H.

doi:10.1083/jcb.113.5.1145

Cited by 254 publications

(128 citation statements)

References 40 publications

(71 reference statements)

Supporting

Mentioning

115

Contrasting

Unclassified

Order By: Relevance

“…Caffeine can also act to antagonize muscarinic-induced 1P3 generation, action, and calcium mobilization (Zacchetti et al, 1991;Brown et al, 1992;Irving et al, 1992;Pozzan et al, 1994). There is also evidence that ryanodine/caffeine-and 1P3 /muscarinic-sensitive calcium release pools are spatially and functionally distinct in a number of secretory cell types and neurons (Walton et al, 1991;Feng et al, 1992;Sharp et al, 1993). Other caffeine actions, such as increases in cyclic AMP concentration and adenosine receptor antagonism (Nehlig et al, 1992), could also affect Aß production or calcium entry (Reddy et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Caffeine Stimulates Amyloid β‐Peptide Release from β‐Amyloid Precursor Protein‐Transfected HEK293 Cells

Querfurth

Jiang²,

Geiger

et al. 1997

Journal of Neurochemistry

View full text Add to dashboard Cite

Extracellular amyloid ß-peptide (Aß) deposition is a pathological feature of Alzheimer's disease and the aging brain. Intracellular Aß accumulation is observed in the human muscle disease, inclusion body myositis. Aß has been reported to be toxic to neurons through disruption of normal calcium homeostasis. The pathogenic role of Aß in inclusion body myositis is not as clear. Elevation of intracellular calcium following application of calcium ionophore increases the generation of Aß from its precursor protein (ßAPP). A receptor-based mechanism for the increase in Aß production has not been reported to our knowledge. Here, we use caffeine to stimulate ryanodine receptor (RYR)-regulated intracellular calcium release channels and show that internal calcium stores also participate in the genesis of Aß. In cultured HEK293 cells transfected with ßAPP cDNA, caffeine (5-10 mM) significantly increased the release of Aß fourfold compared with control. These actions of caffeine were saturable, modulated by ryanodine, and inhibited by the RYR antagonists ruthenium red and procaine. The calcium reuptake inhibitors thapsigargin and cyclopiazonic acid potentiated caffeine-stimulated Aß release. NH 4CI and monensin, agents that alter acidic gradients in intracellular vesicles, abolished both the caffeine and ionophore effects. Immunocytochemical studies showed some correspondence between the distribution patterns of RYR and cellular ßAPP immunoreactivities. The relevance of these findings to Alzheimer's disease and inclusion body myositis is discussed. Key Words: CaffeineAmyloid ß-peptide-ß-Amyloid precursor protein-HEK293 cells-Alzheimer's disease-Inclusion body myositis. J. Neurochem. 69, 1580-1591 (1997).ß-Amyloid-laden plaques and vascular deposits are pathologic hallmarks common to Alzheimer' s disease (AD) and the normal aging process. The 4-kDa amybid ß-peptide (Aß) is a secreted 39-42 amino acid peptide by-product of endocytotic and secretory processes (involving unidentified proteases referred to as ß-and y-secretases) acting on the ß-amyloid precursor protein (ßAPP) . The predominant proteolytic event of ßAPP processing leads to the secretion of a large NH2-terminal ectodomain (ßPP5) (Weidemann et al., 1989;Esch et al., 1990;Sisodia et al., 1990) and retention of a 10-kDa COOHterminal membrane fragment (Selkoe et al., 1988) that is catalyzed by an unknown protease termed a-secretase. The latter scission occurs at Aß position 16, thereby precluding formation of intact Aß (Esch et al., 1990;Oltersdorf et al., 1990), and occurs either at the cell surface or within secretory vesicles targeted for exocytosis (Sisodia et al., 1990;Sambamurti et al., 1992;De Strooper et al., 1993; Haass et al., 1995b). A second trafficking pathway involves the reinternalization of cell surface ßAPP by endosomes that are ultimately targeted to lysosomes (Yamazaki et al., 1995). Constitutive production of Aß from wild-type ßAPP molecules occurs mainly via endocytosis of cell surface-associated ßAPP (Koo and Squazzo, 1994).Aß deposits ...

show abstract

Section: Discussionmentioning

confidence: 99%

Caffeine Stimulates Amyloid β‐Peptide Release from β‐Amyloid Precursor Protein‐Transfected HEK293 Cells

Querfurth

Jiang²,

Geiger

et al. 1997

Journal of Neurochemistry

View full text Add to dashboard Cite

show abstract

“…The RyR isoforms are expressed in the avian central nervous system in specific cells, such as cerebellar Purkinje neurons Walton et al, 1991). Therefore, we investigated whether aRyR is present in these neurons in cdcn cerebella.…”

Section: Lack Of Expression Of Aryr In Cdcn Cerebellamentioning

confidence: 99%

“…Tissues were prepared for electron microscopy as described previously Walton et al, 1991). Leg and breast skeletal muscles from day E l 2 and E l 8 chick embryos were fixed by immersion in 2% glutaraldehyde and 2% formaldehyde buffered with 0.15 M sodium cacodylate, pH 7.4, at 4°C for 2 h. After being washed in 0.15 M sodium cacodylate, the tissues were post-fixed in 1% osmium tetroxide in the same buffer a t 4°C for 1 h. The tissues were rinsed in double distilled water (DDW) and stained en bloc with 1% uranyl acetate in DDW at 4°C for 4 h. After further washing in DDW, the tissue was dehydrated in ethanol, infiltrated wich eponlaraldite resin and polymerized a t 60°C.…”

Section: Electron Microscopymentioning

confidence: 99%

Failure to make normal α ryanodine receptor is an early event associated with the Crooked Neck Dwarf (cn) mutation in chicken

Airey

Baring

Beck

et al. 1993

Developmental Dynamics

View full text Add to dashboard Cite

We have investigated the molecular basis of the Crooked Neck Dwarf (cn) mutation in embryonic chickens. Using biochemical and pharmacological techniques we are unable to detect normal α ryanodine receptor (RyR) protein in intact cn/cn skeletal muscle. Extremely low levels of αRyR immunoreactivity can be observed in mutant muscles, but the distribution of this staining differs from that in normal muscle and colocalizes with the rough endoplasmic reticulum immunoglobulin binding protein, BiP. This suggests the existence of an abnormal αRyR protein in mutant muscle. In day E12 cn/cn muscle the levels of RyR mRNA are reduced by ∼80%, while the levels of other muscle proteins, including the α1 subunit of the dihydropyridine receptor, the SRCa2+‐ATPase, calsequestrin, and glyceraldehyde‐3‐phosphate dehydrogenase, and their associated mRNAs are essentially normal in cn/cn muscle. There is also a failure to express αRyR in cn/cn cerebellar Purkinje neurons. Expression of the βRyR, a second RyR isoform, is not initiated in normal skeletal muscle until day E18. In cn/cn skeletal muscle significant muscle degeneration has occurred by this time and the βRyR is found at low levels in only a subset of fibers suggesting the reduced levels of this isoform are a secondary consequence of the mutation. The cardiac RyR isoform is found in cn/cn cardiac muscle, which contracts in a vigorous manner. In summary, a failure to make normal αRyR receptor appears to be an event closely associated with the cn mutation and one which may be largely responsible for development of the cn/cn phenotype in embryonic skeletal muscle. © 1993 Wiley‐Liss, Inc.

show abstract

“…The first of these is the inositol-1,4, 5-trisphosphate (IP 3 ) receptor 7 , which is synergistically coactivated 8 by IP 3 and Ca 2+ . The IP 3 receptor controls Ca 2+ release from the endoplasmic reticulum and is present in high concentrations in both spines and shafts of Purkinje cell dendrites 9 . IP 3 could be formed via the activation of metabotropic glutamate receptors (mGluR) by glutamate released from PF terminals [10][11][12] .…”

Section: Articlesmentioning

confidence: 99%

Coincidence detection in single dendritic spines mediated by calcium release

2000

View full text Add to dashboard Cite

articlesCentral to understanding learning mechanisms at a synaptic level is the idea that lasting functional change can be driven by the coincidence of multiple signals at a single synaptic site 1 . One candidate for such a change is long-term depression of the parallel fiber input to cerebellar Purkinje cells, a form of synaptic plasticity that is thought to underlie several forms of associative motor learning 2 . LTD is induced by coincident activation of PF and CF synaptic inputs, and can last from hours to days 2,3 .Although LTD has been extensively studied, the identity of the coincidence detection mechanism(s) triggered by conjunctive activation of PF and CF synapses is still controversial 4 . One second messenger, cytosolic calcium (Ca 2+ ), is both necessary 5 and sufficient 6 (L. Khiroug, G. Ellis-Davies & G. J. Augustine, Soc. Neurosci. Abstr. 25, 397.3, 1999) to induce a depression of synaptic strength. This indicates that Ca 2+ is a critical link in the induction of LTD. However, in contrast to most other synapses that show Ca 2+ -dependent associative plasticity, PF synapses lack postsynaptic NMDA receptors, which allow Ca 2+ to enter neurons in response to the simultaneous presence of glutamate and depolarization (for review, see ref. 1).Purkinje cells do, however, possess two other molecular mechanisms that could detect conjunctive PF and CF activation to generate a Ca 2+ signal. The first of these is the inositol-1,4, 5-trisphosphate (IP 3 ) receptor 7 , which is synergistically coactivated 8 by IP 3 and Ca 2+ . The IP 3 receptor controls Ca 2+ release from the endoplasmic reticulum and is present in high concentrations in both spines and shafts of Purkinje cell dendrites 9 . IP 3 could be formed via the activation of metabotropic glutamate receptors (mGluR) by glutamate released from PF terminals 10-12 . The source of Ca 2+ could be voltage-gated Ca 2+ channels, which are known to be located on PF spines 13 , and may even be colocalized with the IP 3 receptor on a molecular scale 14 . The depolarization necessary for activation of these Ca 2+ channels could be provided by the complex spike that is triggered by CF input 15 . This mechanism, therefore, predicts that the combination of CF and PF inputs should generate a supralinear Ca 2+ signal in PF spines 7 .A second potential coincidence detection mechanism uses the voltage-gated Ca 2+ channels in PF spines 13 . Because the channel activation curve is highly nonlinear, even a small local depolarization resulting from activation of AMPA channels at the PF synapse 16 could combine with the depolarization by the complex spike to cause supralinear Ca 2+ influx.The involvement of release through IP 3 receptors in the LTD induction pathway is supported by experiments demonstrating that blockers of Ca 2+ release inhibit LTD 6 , and that IP 3 uncaging can cause a form of LTD 6,11 . The metabotropic pathway is implicated because LTD induction can be prevented by mGluR antagonists 17 (but see also ref. 4), and is impaired in a genetic knockout of mGluR1 ...

show abstract

Ryanodine and inositol trisphosphate receptors coexist in avian cerebellar Purkinje neurons.

Cited by 254 publications

References 40 publications

Caffeine Stimulates Amyloid β‐Peptide Release from β‐Amyloid Precursor Protein‐Transfected HEK293 Cells

Caffeine Stimulates Amyloid β‐Peptide Release from β‐Amyloid Precursor Protein‐Transfected HEK293 Cells

Failure to make normal α ryanodine receptor is an early event associated with the Crooked Neck Dwarf (cn) mutation in chicken

Coincidence detection in single dendritic spines mediated by calcium release

Contact Info

Product

Resources

About