Bidirectional Ca2+ signaling occurs between the endoplasmic reticulum and acidic organelles

The endoplasmic reticulum (ER) and acidic organelles (endo-lysosomes) act as separate Ca2+ stores that release Ca2+ in response to the second messengers IP3 and cADPR (ER) or NAADP (acidic organelles). Typically, trigger Ca2+ released from acidic organelles by NAADP subsequently recruits IP3 or ryanodine receptors on the ER, an anterograde signal important for amplification and Ca2+ oscillations/waves. We therefore investigated whether the ER can signal back to acidic organelles, using organelle pH as a reporter of NAADP action. We show that Ca2+ released from the ER can activate the NAADP pathway in two ways: first, by stimulating Ca2+-dependent NAADP synthesis; second, by activating NAADP-regulated channels. Moreover, the differential effects of EGTA and BAPTA (slow and fast Ca2+ chelators, respectively) suggest that the acidic organelles are preferentially activated by local microdomains of high Ca2+ at junctions between the ER and acidic organelles. Bidirectional organelle communication may have wider implications for endo-lysosomal function as well as the generation of Ca2+ oscillations and waves.

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Sigma 1 Receptor, Cholesterol and Endoplasmic Reticulum Contact Sites

Contact ◽

10.1177/25152564211026505 ◽

2021 ◽

Vol 4 ◽

pp. 251525642110265

Author(s):

Vladimir Zhemkov ◽

Jen Liou ◽

Ilya Bezprozvanny

Keyword(s):

Endoplasmic Reticulum ◽

Protein Composition ◽

Sigma 1 Receptor ◽

Functional Roles ◽

Membrane Contact Sites ◽

Contact Sites ◽

Sigma 1 ◽

Membrane Contact ◽

Organelle Communication ◽

Cellular Organelles

Recent studies indicated potential importance of membrane contact sites (MCS) between the endoplasmic reticulum (ER) and other cellular organelles. These MCS have unique protein and lipid composition and serve as hubs for inter-organelle communication and signaling. Despite extensive investigation of MCS protein composition and functional roles, little is known about the process of MCS formation. In this perspective, we propose a hypothesis that MCS are formed not as a result of random interactions between membranes of ER and other organelles but on the basis of pre-existing cholesterol-enriched ER microdomains.

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All Hands on Deck—The Role of Chloroplasts, Endoplasmic Reticulum, and the Nucleus in Driving Plant Innate Immunity

Molecular Plant-Microbe Interactions ◽

10.1094/mpmi-05-10-0113 ◽

2010 ◽

Vol 23 (11) ◽

pp. 1368-1380 ◽

Cited By ~ 55

Author(s):

Meenu S. Padmanabhan ◽

S. P. Dinesh-Kumar

Keyword(s):

Innate Immunity ◽

Endoplasmic Reticulum ◽

Second Messengers ◽

Defense Responses ◽

Plant Innate Immunity ◽

Er Quality Control ◽

Immune Modulators ◽

Immune Receptors ◽

Cytoplasmic Transport

Plant innate immunity is mediated by cell membrane and intracellular immune receptors that function in distinct and overlapping cell-signaling pathways to activate defense responses. It is becoming increasingly evident that immune receptors rely on components from multiple organelles for the generation of appropriate defense responses. This review analyzes the defense-related functions of the chloroplast, nucleus, and endoplasmic reticulum (ER) during plant innate immunity. It details the role of the chloroplasts in synthesizing defense-specific second messengers and discusses the retrograde signal transduction pathways that exist between the chloroplast and nucleus. Because the activities of immune modulators are regulated, in part, by their subcellular localization, the review places special emphasis on the dynamics and nuclear–cytoplasmic transport of immune receptors and regulators and highlights the importance of this process in generating orderly events during an innate immune response. The review also covers the recently discovered contributions of the ER quality-control pathways in ensuring the signaling competency of cell surface immune receptors or immune regulators.

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Acidocalcisomes in Toxoplasma gondii tachyzoites

Biochemical Journal ◽

10.1042/bj3130655 ◽

1996 ◽

Vol 313 (2) ◽

pp. 655-659 ◽

Cited By ~ 106

Author(s):

Silvia N. J. MORENO ◽

Li ZHONG

Keyword(s):

Endoplasmic Reticulum ◽

Toxoplasma Gondii ◽

Mammalian Cells ◽

Specific Inhibitor ◽

Mitochondrial Atpase ◽

Bafilomycin A1 ◽

Atpase Inhibitor ◽

Extracellular Medium ◽

Acidic Compartment ◽

Acidic Organelles

Toxoplasma gondii tachyzoites were loaded with the fluorescent indicator fura 2 to investigate the transport mechanisms involved in maintaining their intracellular Ca2+ homoeostasis. The mitochondrial ATPase inhibitor oligomycin and the endoplasmic-reticulum Ca2+-ATPase inhibitor thapsigargin increased the intracellular Ca2+ concentration ([Ca2+]i), thus indicating the requirement for ATP and the involvement of the endoplasmic reticulum in maintaining intracellular Ca2+ homoeostasis. The effect of thapsigargin was more accentuated in the presence of extracellular Ca2+, clearly showing that, as occurs with other eukaryotic cells, depletion of intracellular Ca2+ pools led to an increase in the uptake of Ca2+ from the extracellular medium. In addition to these results, we found evidence that, in contrast with what occurs in mammalian cells, T. gondii tachyzoites possess a significant amount of Ca2+ stored in an acidic compartment, termed the acidocalcisome, as indicated by: (1) the increase in [Ca2+]i induced by bafilomycin A1 (a specific inhibitor of H+-ATPases), nigericin (a K+/H+ exchanger) or the weak base NH4Cl, in the nominal absence of extracellular Ca2+ to preclude Ca2+ entry; and (2) the effect of ionomycin, a Ca2+-releasing ionophore that cannot take Ca2+ out of acidic organelles and that was more effective after alkalinization of these compartments by addition of bafilomycin A1, nigericin or NH4Cl. Considering the relative importance of the ionomycin-releasable and the ionomycin+NH4Cl-releasable Ca2+ pools, it is apparent that T. gondii tachyzoites contain a significant amount of Ca2+ stored in acidocalcisomes.

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Calcium Signals in Nerve Cells

Physiology ◽

10.1152/physiologyonline.1991.6.1.6 ◽

1991 ◽

Vol 6 (1) ◽

pp. 6-10 ◽

Cited By ~ 1

Author(s):

PG Kostyuk ◽

AV Tepikin

Keyword(s):

Endoplasmic Reticulum ◽

Ion Channels ◽

Nerve Cell ◽

Second Messengers ◽

Cell Activity ◽

Nerve Cells ◽

Calcium Signals ◽

Intracellular Ca ◽

Ca Ions

Increases in intracellular Ca ions follow each cycle of nerve cell activity. Sources of Ca are voltage- and receptor-operated membrane ion channels and endoplasmic reticulum (ER). Ca release from ER can be triggered by different second messengers, and uptake into the ER can terminate the Ca signal.

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Alterations of the Endoplasmic Reticulum (ER) Calcium Signaling Molecular Components in Alzheimer’s Disease

Cells ◽

10.3390/cells9122577 ◽

2020 ◽

Vol 9 (12) ◽

pp. 2577

Author(s):

Mounia Chami ◽

Frédéric Checler

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Endoplasmic Reticulum ◽

Ryanodine Receptors ◽

Functional Consequences ◽

Intracellular Organelles ◽

And Function ◽

Molecular Components ◽

Cellular Components ◽

Er Calcium

Sustained imbalance in intracellular calcium (Ca2+) entry and clearance alters cellular integrity, ultimately leading to cellular homeostasis disequilibrium and cell death. Alzheimer’s disease (AD) is the most common cause of dementia. Beside the major pathological features associated with AD-linked toxic amyloid beta (Aβ) and hyperphosphorylated tau (p-tau), several studies suggested the contribution of altered Ca2+ handling in AD development. These studies documented physical or functional interactions of Aβ with several Ca2+ handling proteins located either at the plasma membrane or in intracellular organelles including the endoplasmic reticulum (ER), considered the major intracellular Ca2+ pool. In this review, we describe the cellular components of ER Ca2+ dysregulations likely responsible for AD. These include alterations of the inositol 1,4,5-trisphosphate receptors’ (IP3Rs) and ryanodine receptors’ (RyRs) expression and function, dysfunction of the sarco-endoplasmic reticulum Ca2+ ATPase (SERCA) activity and upregulation of its truncated isoform (S1T), as well as presenilin (PS1, PS2)-mediated ER Ca2+ leak/ER Ca2+ release potentiation. Finally, we highlight the functional consequences of alterations of these ER Ca2+ components in AD pathology and unravel the potential benefit of targeting ER Ca2+ homeostasis as a tool to alleviate AD pathogenesis.

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Isoflurane induces endoplasmic reticulum stress and caspase activation through ryanodine receptors

British Journal of Anaesthesia ◽

10.1093/bja/aeu053 ◽

2014 ◽

Vol 113 (4) ◽

pp. 695-707 ◽

Cited By ~ 20

Author(s):

H. Wang ◽

Y. Dong ◽

J. Zhang ◽

Z. Xu ◽

G. Wang ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Endoplasmic Reticulum Stress ◽

Ryanodine Receptors ◽

Caspase Activation

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Release of Ca2+ from intracellular organelles by peptide analogues: evidence against involvement of metalloendoproteases in Ca2+ sequestration by the endoplasmic reticulum

Biochemical Journal ◽

10.1042/bj3040499 ◽

1994 ◽

Vol 304 (2) ◽

pp. 499-507 ◽

Cited By ~ 3

Author(s):

M A Brostrom ◽

W L Wong Ling ◽

D Gmitter ◽

C O Brostrom

Keyword(s):

Endoplasmic Reticulum ◽

Ryanodine Receptors ◽

Pituitary Cells ◽

Peptide Bonds ◽

High Affinity ◽

Synthesis And Processing ◽

Internal Peptide ◽

Competitive Substrate ◽

Nitrophenyl Ester ◽

Peptide Analogues

N-Benzyloxycarbonyl-Gly-Phe-amide (Z-Gly-Phe-NH2), a competitive substrate for metalloendoproteases, mobilizes intracellular Ca2+ and suppresses protein synthesis and processing in a Ca(2+)-dependent, reversible manner. To ascertain whether Z-Gly-Phe-NH2 acts as Ca(2+)-storing organelles, effects of the dipeptide on Ca2+ sequestration by saponin-porated GH3 pituitary cells were examined. Porated preparations sequestered Ca2+ into two compartments with different Ca2+ affinities. Ca2+ accumulation at nM concentrations of free Ca2+ was inhibited by thapsigargin and inositol 1,4,5-triphosphate [Ins(1,4,5)P3], enhanced by oxalate and unaffected by oligomycin. Cation accumulation at microM concentrations of free Ca2+ was sensitive to oligomycin but not to thapsigargin. Z-Gly-Phe-NH2 reduced Ca2+ sequestration by both compartments. The dipeptide mobilized Ca2+ from the high-affinity compartment within 1-2 min without affecting Ca2+ uptake. Ca2+ was mobilized more rapidly by Z-Gly-Phe-NH2 and thapsigargin together than by either agent alone. The presence of a thiol-reducing agent was required for Ca2+ mobilization by Z-Gly-Phe-NH2 but not by thapsigargin or Ins(1,4,5)P3. Ca2+ mobilization by Z-Gly-Phe-NH2 could not be attributed to effects on anion-permeability or to actions at Ins(1,4,5)P3 or ryanodine receptors. Results with assorted peptide analogues did not favour suppression of metalloendoprotease activity in the Ca(2+)-mobilizing action of Z-Gly-Phe-NH2. The more hydrophobic analogue Z-L-Tyr-p-nitrophenyl ester was 60-80-fold more potent in mobilizing Ca2+ from intact and porated cells and perturbed the high-affinity Ca(2+)-sequestering compartment selectively. Z-Gly-Phe-NH2 and Z-L-Tyr-p-nitrophenyl ester are proposed to release Ca2+ from the endoplasmic reticulum through an ion pore with affinity for hydrophobic molecules containing internal peptide bonds.

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Ca2+ accumulation into acidic organelles mediated by Ca2+- and vacuolar H+-ATPases in human platelets

Biochemical Journal ◽

10.1042/bj20050168 ◽

2005 ◽

Vol 390 (1) ◽

pp. 243-252 ◽

Cited By ~ 96

Author(s):

José J. López ◽

Cristina Camello-Almaraz ◽

José A. Pariente ◽

Ginés M. Salido ◽

Juan A. Rosado

Keyword(s):

Endoplasmic Reticulum ◽

Arginine Vasopressin ◽

Previous Treatment ◽

Human Platelets ◽

Bafilomycin A1 ◽

Cellular Processes ◽

Tubular System ◽

Intracellular Compartments ◽

Functional Relevance ◽

Acidic Organelles

Most physiological agonists increase cytosolic free [Ca2+]c (cytosolic free Ca2+ concentration) to regulate a variety of cellular processes. How different stimuli evoke distinct spatiotemporal Ca2+ responses remains unclear, and the presence of separate intracellular Ca2+ stores might be of great functional relevance. Ca2+ accumulation into intracellular compartments mainly depends on the activity of Ca2+- and H+-ATPases. Platelets present two separate Ca2+ stores differentiated by the distinct sensitivity to thapsigargin and TBHQ [2,5-di-(t-butyl)-1,4-hydroquinone]. Although one store has long been identified as the dense tubular system, the nature of the TBHQ-sensitive store remains uncertain. Treatment of platelets with GPN (glycylphenylalanine-2-naphthylamide) impaired Ca2+ release by TBHQ and reduced that evoked by thrombin. In contrast, GPN did not modify Ca2+ mobilization stimulated by ADP or AVP ([arginine]vasopressin). Treatment with nigericin, a proton carrier, and bafilomycin A1, an inhibitor of the vacuolar H+-ATPase, to dissipate the proton gradient into acidic organelles induces a transient increase in [Ca2+]c that was abolished by previous treatment with the SERCA (sarcoplasmic/endoplasmic-reticulum Ca2+-ATPase) 3 inhibitor TBHQ. Depleted acidic stores after nigericin or bafilomycin A1 were refilled by SERCA 3. Thrombin, but not ADP or AVP, reduces the rise in [Ca2+]c evoked by nigericin and bafilomycin A1. Our results indicate that the TBHQ-sensitive store in human platelets is an acidic organelle whose Ca2+ accumulation is regulated by both Ca2+- and vacuolar H+-ATPases.

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