scholarly journals STIM1L is a new actin-binding splice variant involved in fast repetitive Ca2+ release

2011 ◽  
Vol 194 (2) ◽  
pp. 335-346 ◽  
Author(s):  
Basile Darbellay ◽  
Serge Arnaudeau ◽  
Charles R. Bader ◽  
Stephane Konig ◽  
Laurent Bernheim
Keyword(s):  
Plasma Membrane ◽  
Intracellular Signaling ◽  
Cell Types ◽  
Actin Binding ◽  
Slow Process ◽  
Excitable Cells ◽  
Store Depletion ◽  
Mammalian Tissues ◽  
New Protein ◽  
Ca2 Channels

Cytosolic Ca2+ signals encoded by repetitive Ca2+ releases rely on two processes to refill Ca2+ stores: Ca2+ reuptake from the cytosol and activation of a Ca2+ influx via store-operated Ca2+ entry (SOCE). However, SOCE activation is a slow process. It is delayed by >30 s after store depletion because stromal interaction molecule 1 (STIM1), the Ca2+ sensor of the intracellular stores, must form clusters and migrate to the membrane before being able to open Orai1, the plasma membrane Ca2+ channel. In this paper, we identify a new protein, STIM1L, that colocalizes with Orai1 Ca2+ channels and interacts with actin to form permanent clusters. This property allowed the immediate activation of SOCE, a characteristic required for generating repetitive Ca2+ signals with frequencies within seconds such as those frequently observed in excitable cells. STIM1L was expressed in several mammalian tissues, suggesting that many cell types rely on this Ca2+ sensor for their Ca2+ homeostasis and intracellular signaling.

Mechanisms of capacitative calcium entry

2001 ◽  
Vol 114 (12) ◽  
pp. 2223-2229 ◽  
Author(s):  
James W. Putney ◽  
Lisa M. Broad ◽  
Franz-Josef Braun ◽  
Jean-Philippe Lievremont ◽  
Gary St J. Bird
Keyword(s):  
Plasma Membrane ◽  
Phospholipase C ◽  
Binding Sites ◽  
Cell Types ◽  
Store Depletion ◽  
Blocking Effects ◽  
Conformational Coupling ◽  
Phosphatidylinositol 4 ◽  
Filling State ◽  
Ca2 Channels

Capacitative Ca2+ entry involves the regulation of plasma membrane Ca2+ channels by the filling state of intracellular Ca2+ stores in the endoplasmic reticulum (ER). Several theories have been advanced regarding the mechanism by which the stores communicate with the plasma membrane. One such mechanism, supported by recent findings, is conformational coupling: inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) receptors in the ER may sense the fall in Ca2+ levels through Ca2+-binding sites on their lumenal domains, and convey this conformational information directly by physically interacting with Ca2+ channels in the plasma membrane. In support of this idea, in some cell types, store-operated channels in excised membrane patches appear to depend on the presence of both Ins(1,4,5)P3 and Ins(1,4,5)P3 receptors for activity; in addition, inhibitors of Ins(1,4,5)P3 production that either block phospholipase C or inhibit phosphatidylinositol 4-kinase can block capacitative Ca2+ entry. However, the electrophysiological current underlying capacitative Ca2+ entry is not blocked by an Ins(1,4,5)P3 receptor antagonist, and the blocking effects of a phospholipase C inhibitor are not reversed by the intracellular application of Ins(1,4,5)P3. Furthermore, cells whose Ins(1,4,5)P3 receptor genes have been disrupted can nevertheless maintain their capability to activate capacitative Ca2+ entry channels in response to store depletion. A tentative conclusion is that multiple mechanisms for signaling capacitative Ca2+ entry may exist, and involve conformational coupling in some cell types and perhaps a diffusible signal in others.

Calcium entry and the control of calcium oscillations

2003 ◽  
Vol 31 (5) ◽  
pp. 916-919 ◽  
Author(s):  
T.J. Shuttleworth ◽  
O. Mignen
Keyword(s):  
Arachidonic Acid ◽  
Critical Role ◽  
Cell Types ◽  
Calcium Entry ◽  
Calcium Oscillations ◽  
Reciprocal Regulation ◽  
Crac Channels ◽  
Store Depletion ◽  
Low Concentrations ◽  
Ca2 Channels

During oscillatory Ca2+ signals, the agonist-induced enhanced entry of extracellular Ca2+ plays a critical role in modulating the frequency of the oscillations. Although it was originally assumed that the entry of Ca2+ under these conditions occurred via the well-known, and apparently ubiquitous, store-operated mechanism, subsequent studies suggested that this was unlikely. It is now known that, in many cell types, a novel non-capacitative Ca2+-selective pathway whose activation is dependent on arachidonic acid is responsible, and the channels involved [ARC channels (arachidonate-regulated Ca2+ channels)] have been characterized. These ARC channels co-exist with the store-operated CRAC channels (Ca2+-release-activated Ca2+ channel) in cells, but each plays a unique and non-overlapping role in Ca2+ signalling. In particular, it is the ARC channels that are specifically activated at the low agonist concentrations that give rise to oscillatory Ca2+ signals and provide the predominant mode of Ca2+ entry under these conditions. The indications are that Ca2+ entry through the ARC channels increases the likelihood that low concentrations of Ins(1,4,5)P3 will trigger repetitive Ca2+ release. At higher agonist concentrations, store-depletion is more complete and sustained resulting in the activation of CRAC channels. At the same time the ARC channels are turned off, resulting in what we have described as a reciprocal regulation of these two distinct Ca2+ entry pathways.

scholarly journals Junctophilin-4, a component of the endoplasmic reticulum–plasma membrane junctions, regulates Ca2+ dynamics in T cells

2016 ◽  
Vol 113 (10) ◽  
pp. 2762-2767 ◽  
Author(s):  
Jin Seok Woo ◽  
Sonal Srikanth ◽  
Miyuki Nishi ◽  
Peipei Ping ◽  
Hiroshi Takeshima ◽  
...  
Keyword(s):  
T Cells ◽  
Endoplasmic Reticulum ◽  
Plasma Membrane ◽  
Genetic Manipulation ◽  
Erk Signaling ◽  
Excitable Cells ◽  
Activated T Cells ◽  
Activation Markers ◽  
Extracellular Signaling ◽  
Store Depletion

Orai1 and stromal interaction molecule 1 (STIM1) mediate store-operated Ca2+ entry (SOCE) in immune cells. STIM1, an endoplasmic reticulum (ER) Ca2+ sensor, detects store depletion and interacts with plasma membrane (PM)-resident Orai1 channels at the ER–PM junctions. However, the molecular composition of these junctions in T cells remains poorly understood. Here, we show that junctophilin-4 (JP4), a member of junctional proteins in excitable cells, is expressed in T cells and localized at the ER–PM junctions to regulate Ca2+ signaling. Silencing or genetic manipulation of JP4 decreased ER Ca2+ content and SOCE in T cells, impaired activation of the nuclear factor of activated T cells (NFAT) and extracellular signaling-related kinase (ERK) signaling pathways, and diminished expression of activation markers and cytokines. Mechanistically, JP4 directly interacted with STIM1 via its cytoplasmic domain and facilitated its recruitment into the junctions. Accordingly, expression of this cytoplasmic fragment of JP4 inhibited SOCE. Furthermore, JP4 also formed a complex with junctate, a Ca2+-sensing ER-resident protein, previously shown to mediate STIM1 recruitment into the junctions. We propose that the junctate–JP4 complex located at the junctions cooperatively interacts with STIM1 to maintain ER Ca2+ homeostasis and mediate SOCE in T cells.

Regulation of Ca2+ release-activated Ca2+channels by INAD and Ca2+ influx factor

2003 ◽  
Vol 284 (2) ◽  
pp. C497-C505 ◽  
Author(s):  
Zhengchang Su ◽  
Douglas S. Barker ◽  
Peter Csutora ◽  
Theresa Chang ◽  
Richard L. Shoemaker ◽  
...  
Keyword(s):  
Cell Types ◽  
Model System ◽  
Low Molecular Weight ◽  
Coupling Mechanism ◽  
Crac Channels ◽  
Store Depletion ◽  
Drosophila Protein ◽  
Mammalian Homologue ◽  
Trisphosphate Receptor ◽  
Ca2 Channels

The coupling mechanism between depletion of Ca2+ stores in the endoplasmic reticulum and plasma membrane store-operated ion channels is fundamental to Ca2+ signaling in many cell types and has yet to be completely elucidated. Using Ca2+release-activated Ca2+ (CRAC) channels in RBL-2H3 cells as a model system, we have shown that CRAC channels are maintained in the closed state by an inhibitory factor rather than being opened by the inositol 1,4,5-trisphosphate receptor. This inhibitory role can be fulfilled by the Drosophila protein INAD (inactivation-no after potential D). The action of INAD requires Ca2+ and can be reversed by a diffusible Ca2+ influx factor. Thus the coupling between the depletion of Ca2+ stores and the activation of CRAC channels may involve a mammalian homologue of INAD and a low-molecular-weight, diffusible store-depletion signal.

scholarly journals Dynamin Is Required for GnRH Signaling to L-Type Calcium Channels and Activation of ERK

Endocrinology ◽  
2015 ◽  
Vol 157 (2) ◽  
pp. 831-843 ◽  
Author(s):  
Brian S. Edwards ◽  
An K. Dang ◽  
Dilyara A. Murtazina ◽  
Melissa G. Dozier ◽  
Jennifer D. Whitesell ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Green Fluorescent Protein ◽  
Actin Cytoskeleton ◽  
Fluorescent Protein ◽  
Leading Edge ◽  
Dominant Negative ◽  
Actin Binding ◽  
Erk Phosphorylation ◽  
Green Fluorescent ◽  
Ca2 Channels

Abstract We have shown that GnRH-mediated engagement of the cytoskeleton induces cell movement and is necessary for ERK activation. It also has previously been established that a dominant negative form of the mechano-GTPase dynamin (K44A) attenuates GnRH activation of ERK. At present, it is not clear at what level these cellular events might be linked. To explore this, we used live cell imaging in the gonadotrope-derived αT3–1 cell line to determine that dynamin-green fluorescent protein accumulated in GnRH-induced lamellipodia and plasma membrane protrusions. Coincident with translocation of dynamin-green fluorescent protein to the plasma membrane, we demonstrated that dynamin colocalizes with the actin cytoskeleton and the actin binding protein, cortactin at the leading edge of the plasma membrane. We next wanted to assess the physiological significance of these findings by inhibiting dynamin GTPase activity using dynasore. We find that dynasore suppresses activation of ERK, but not c-Jun N-terminal kinase, after exposure to GnRH agonist. Furthermore, exposure of αT3–1 cells to dynasore inhibited GnRH-induced cyto-architectural rearrangements. Recently it has been discovered that GnRH induced Ca2+ influx via the L-type Ca2+ channels requires an intact cytoskeleton to mediate ERK phosphorylation. Interestingly, not only does dynasore attenuate GnRH-mediated actin reorganization, it also suppresses Ca2+ influx through L-type Ca2+ channels visualized in living cells using total internal reflection fluorescence microscopy. Collectively, our data suggest that GnRH-induced membrane remodeling events are mediated in part by the association of dynamin and cortactin engaging the actin cytoskeleton, which then regulates Ca2+ influx via L-type channels to facilitate ERK phosphorylation.

Isolation and characterization of monoclonal antibodies directed against novel components of macrophage phagosomes

1999 ◽  
Vol 112 (24) ◽  
pp. 4705-4713 ◽  
Author(s):  
N.S. Morrissette ◽  
E.S. Gold ◽  
J. Guo ◽  
J.A. Hamerman ◽  
A. Ozinsky ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Plasma Membrane ◽  
Magnetic Beads ◽  
Cell Clone ◽  
Cell Types ◽  
Peritoneal Macrophages ◽  
Actin Binding ◽  
Isolation And Characterization ◽  
Macrophage Phagocytosis

In order to identify novel proteins associated with various stages of macrophage phagocytosis, we have generated monoclonal antibodies that recognize phagosomes. Purified Fc receptor-mediated phagosomes, isolated by feeding IgG-conjugated magnetic beads to LPS-primed murine peritoneal macrophages, were used as the immunogen. An immunofluorescence screen was used to isolate and single-cell clone approximately 150 monoclonal antibodies that recognize mouse macrophage phagosomes as well as labeling other cellular components in patterns which are frequently distinct from those observed with previously characterized phagosome-associated proteins. Predominant morphological categories (in addition to phagosome labeling) include staining of one or more of the following: cytoskeletal patterns, vesicular patterns and plasma membrane localization. In this paper, we describe the antibody screen, preliminary characterization of the antibodies and our identification of the antigens for three representative monoclonal antibodies. These antibodies identify a plasma membrane associated receptor (Mac-1, a subunit of the complement receptor), an actin binding protein (coronin-2) and a vesicular protein (amphiphysin II). Some of the antibodies recognize many cell types, whereas other antibodies are apparently macrophage specific as assessed by flow cytometry and histology. Remarkably, several of the antibodies cross-react with the phagocytic slime mold, Dictyostelium discoideum, recognizing phagosomes and other cellular elements as assessed by immunofluorescence and immunoblots. These results indicate that macrophage phagocytosis has both conserved ancestral features and unique specialized aspects associated with the role of these phagocytes in immunity.

scholarly journals S-acylation of Orai1 regulates store-operated Ca2+ entry

2021 ◽  
Vol 135 (5) ◽  
Author(s):  
Savannah J. West ◽  
Goutham Kodakandla ◽  
Qioachu Wang ◽  
Ritika Tewari ◽  
Michael X. Zhu ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Plasma Membrane ◽  
Cell Types ◽  
Central Component ◽  
Channel Activation ◽  
Crac Channels ◽  
Store Depletion ◽  
Crac Channel ◽  
Underlying Mechanisms ◽  
Different Cell Types

ABSTRACT Store-operated Ca2+ entry is a central component of intracellular Ca2+ signaling pathways. The Ca2+ release-activated channel (CRAC) mediates store-operated Ca2+ entry in many different cell types. The CRAC channel is composed of the plasma membrane (PM)-localized Orai1 channel and endoplasmic reticulum (ER)-localized STIM1 Ca2+ sensor. Upon ER Ca2+ store depletion, Orai1 and STIM1 form complexes at ER–PM junctions, leading to the formation of activated CRAC channels. Although the importance of CRAC channels is well described, the underlying mechanisms that regulate the recruitment of Orai1 to ER–PM junctions are not fully understood. Here, we describe the rapid and transient S-acylation of Orai1. Using biochemical approaches, we show that Orai1 is rapidly S-acylated at cysteine 143 upon ER Ca2+ store depletion. Importantly, S-acylation of cysteine 143 is required for Orai1-mediated Ca2+ entry and recruitment to STIM1 puncta. We conclude that store depletion-induced S-acylation of Orai1 is necessary for recruitment to ER–PM junctions, subsequent binding to STIM1 and channel activation.

scholarly journals The life cycle of voltage-gated Ca2+ channels in neurons: an update on the trafficking of neuronal calcium channels

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Laurent Ferron ◽  
Saloni Koshti ◽  
Gerald W. Zamponi
Keyword(s):  
Plasma Membrane ◽  
Intracellular Signaling ◽  
Critical Role ◽  
Functional Expression ◽  
Current Evidence ◽  
Precise Control ◽  
Channel Trafficking ◽  
Voltage Gated ◽  
Cellular Excitability ◽  
Ca2 Channels

Abstract Neuronal voltage-gated Ca2+ (CaV) channels play a critical role in cellular excitability, synaptic transmission, excitation–transcription coupling and activation of intracellular signaling pathways. CaV channels are multiprotein complexes and their functional expression in the plasma membrane involves finely tuned mechanisms, including forward trafficking from the endoplasmic reticulum (ER) to the plasma membrane, endocytosis and recycling. Whether genetic or acquired, alterations and defects in the trafficking of neuronal CaV channels can have severe physiological consequences. In this review, we address the current evidence concerning the regulatory mechanisms which underlie precise control of neuronal CaV channel trafficking and we discuss their potential as therapeutic targets.

Membrane microdomains: lessons from microscopy

1995 ◽  
Vol 53 ◽  
pp. 776-777
Author(s):  
J.M. Robinson ◽  
J.M Oliver
Keyword(s):  
Spatial Distribution ◽  
Plasma Membrane ◽  
Epithelial Cells ◽  
Plasma Membranes ◽  
Cell Types ◽  
Imaging Modalities ◽  
Membrane Microdomains ◽  
Membrane Domains ◽  
Lateral Heterogeneity ◽  
Functional Importance

Specialized regions of plasma membranes displaying lateral heterogeneity are the focus of this Symposium. Specialized membrane domains are known for certain cell types such as differentiated epithelial cells where lateral heterogeneity in lipids and proteins exists between the apical and basolateral portions of the plasma membrane. Lateral heterogeneity and the presence of microdomains in membranes that are uniform in appearance have been more difficult to establish. Nonetheless a number of studies have provided evidence for membrane microdomains and indicated a functional importance for these structures.This symposium will focus on the use of various imaging modalities and related approaches to define membrane microdomains in a number of cell types. The importance of existing as well as emerging imaging technologies for use in the elucidation of membrane microdomains will be highlighted. The organization of membrane microdomains in terms of dimensions and spatial distribution is of considerable interest and will be addressed in this Symposium.

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