Regulation of Store-Operated Ca2+ Entry by Septins

Deb, Bipan Kumar; Hasan, Gaiti

doi:10.3389/fcell.2016.00142

Cited by 23 publications

(19 citation statements)

References 61 publications

(85 reference statements)

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“…Thus, septin-dependent spatial regulation of ER-PM contact sites may be critical to modulate these cellular processes. For example, septins in metazoans regulate, via an as-yet unknown mechanism (46), the interaction between STIM1 and ORAI1, a PM calcium channel, which enables calcium entry upon activation (47). Since STIM1 contains both the ER TMD and PM-binding domains, our study predicts that septin-dependent restriction of STIM1's localization likely regulates the interaction with ORAI1 and thereby intracellular calcium concentration.…”

Section: Discussionmentioning

confidence: 80%

Distinct segregation patterns of yeast cell-peripheral proteins uncovered by a method for protein segregatome analysis

Sugiyama

Tanaka

2019

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

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Protein segregation contributes to various cellular processes such as polarization, differentiation, and aging. However, the difficulty in global determination of protein segregation hampers our understanding of its mechanisms and physiological roles. Here, by developing a quantitative proteomics technique, we globally monitored segregation of preexisting and newly synthesized proteins during cell division of budding yeast, and identified crucial domains that determine the segregation of cell-peripheral proteins. Remarkably, the proteomic and subsequent microscopic analyses demonstrated that the flow through the bud neck of the proteins that harbor both endoplasmic reticulum (ER) membrane-spanning and plasma membrane (PM)-binding domains is not restricted by the previously suggested ER membrane or PM diffusion barriers but by septin-mediated partitioning of the PM-associated ER (pmaER). Furthermore, the proteomic analysis revealed that although the PM-spanning t-SNARE Sso2 was retained in mother cells, its paralog Sso1 unexpectedly showed symmetric localization. We found that the transport of Sso1 to buds was required for enhancement of polarized cell growth and resistance to cell-wall stress. Taken together, these data resolve long-standing questions about septin-mediated compartmentalization of the cell periphery, and provide new mechanistic insights into the segregation of cell-periphery proteins and their cellular functions.

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Section: Discussionmentioning

confidence: 80%

Distinct segregation patterns of yeast cell-peripheral proteins uncovered by a method for protein segregatome analysis

Sugiyama

Tanaka

2019

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

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“…Notably, the foci enriched in septins are spatially separated from STIM1/Orai1 clusters and in relation to the specific septin subform, impose different functional consequences on SOCE yet accomplished in an indirect manner [ 75 , 76 ]. For a detailed review of the role of septins in SOCE, see Deb et al, 2016 [ 77 ]. The septins SEPT2, SEPT4 and SEPT5, collectively constituting filament-forming GTPases, were, according to analysis in Jurkat T lymphocytes and HeLa cells, implicated as positive modulators of SOCE ( Figure 1 ).…”

Section: Regulators Of Crac Channel Functionmentioning

confidence: 99%

More Than Just Simple Interaction between STIM and Orai Proteins: CRAC Channel Function Enabled by a Network of Interactions with Regulatory Proteins

Berlansky

Humer

Sallinger

et al. 2021

IJMS

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The calcium-release-activated calcium (CRAC) channel, activated by the release of Ca2+ from the endoplasmic reticulum (ER), is critical for Ca2+ homeostasis and active signal transduction in a plethora of cell types. Spurred by the long-sought decryption of the molecular nature of the CRAC channel, considerable scientific effort has been devoted to gaining insights into functional and structural mechanisms underlying this signalling cascade. Key players in CRAC channel function are the Stromal interaction molecule 1 (STIM1) and Orai1. STIM1 proteins span through the membrane of the ER, are competent in sensing luminal Ca2+ concentration, and in turn, are responsible for relaying the signal of Ca2+ store-depletion to pore-forming Orai1 proteins in the plasma membrane. A direct interaction of STIM1 and Orai1 allows for the re-entry of Ca2+ from the extracellular space. Although much is already known about the structure, function, and interaction of STIM1 and Orai1, there is growing evidence that CRAC under physiological conditions is dependent on additional proteins to function properly. Several auxiliary proteins have been shown to regulate CRAC channel activity by means of direct interactions with STIM1 and/or Orai1, promoting or hindering Ca2+ influx in a mechanistically diverse manner. Various proteins have also been identified to exert a modulatory role on the CRAC signalling cascade although inherently lacking an affinity for both STIM1 and Orai1. Apart from ubiquitously expressed representatives, a subset of such regulatory mechanisms seems to allow for a cell-type-specific control of CRAC channel function, considering the rather restricted expression patterns of the specific proteins. Given the high functional and clinical relevance of both generic and cell-type-specific interacting networks, the following review shall provide a comprehensive summary of regulators of the multilayered CRAC channel signalling cascade. It also includes proteins expressed in a narrow spectrum of cells and tissues that are often disregarded in other reviews of similar topics.

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“…Septins were shown to regulate SOCE in both non-excitable mammalian cells (Sharma et al, 2013 ) and Drosophila neurons (Deb and Hasan, 2016 , 2019 ; Deb et al, 2016 , 2020 ). In Drosophila , septins are classified into several groups: dSEPT1, dSEPT2, dSEPT4, dSEPT5 and dSEPT7.…”

Section: Stim Interacting Proteinsmentioning

confidence: 99%

“…The simultaneous knockdown of dSEPT1 and dSEPT4 reduced SOCE in Drosophila flight circuit neurons (Deb et al, 2016 ). The knockdown of these subgroups results in the loss of septin filaments and loss of the diffusion barrier, which has a negative influence on Orai activation by STIM (Deb and Hasan, 2016 ). dSEPT1 and dSEPT4 appear to function as positive regulators of SOCE in Drosophila neurons (Deb et al, 2016 ; Deb and Hasan, 2019 ).…”

Section: Stim Interacting Proteinsmentioning

confidence: 99%

“…Similarly, SEPT4 regulates the number of the ER-PM junctions and enhances STIM1-Orai1 interactions within junctions in human cells (Katz et al, 2019 ). Store-independent dOrai Ca 2+ influx results in higher cytosolic Ca 2+ concentrations in resting neurons (Deb and Hasan, 2016 ). The loss of dSEPT7 influences the constitutive activation of Orai channels in resting neurons by uncoupling septin heteromers from ER-PM junctions, thus allowing the STIM interaction with Orai (Deb et al, 2016 , 2020 ).…”

Section: Stim Interacting Proteinsmentioning

confidence: 99%

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Target Molecules of STIM Proteins in the Central Nervous System

Serwach

Gruszczynska-Biegala

2020

Front. Mol. Neurosci.

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Stromal interaction molecules (STIMs), including STIM1 and STIM2, are single-pass transmembrane proteins that are located predominantly in the endoplasmic reticulum (ER). They serve as calcium ion (Ca2+) sensors within the ER. In the central nervous system (CNS), they are involved mainly in Orai-mediated store-operated Ca2+ entry (SOCE). The key molecular components of the SOCE pathway are well-characterized, but the molecular mechanisms that underlie the regulation of this pathway need further investigation. Numerous intracellular target proteins that are located in the plasma membrane, ER, cytoskeleton, and cytoplasm have been reported to play essential roles in concert with STIMs, such as conformational changes in STIMs, their translocation, the stabilization of their interactions with Orai, and the activation of other channels. The present review focuses on numerous regulators, such as Homer, SOCE-associated regulatory factor (SARAF), septin, synaptopodin, golli proteins, partner of STIM1 (POST), and transcription factors and proteasome inhibitors that regulate STIM-Orai interactions in the CNS. Further we describe novel roles of STIMs in mediating Ca2+ influx via other than Orai pathways, including TRPC channels, VGCCs, AMPA and NMDA receptors, and group I metabotropic glutamate receptors. This review also summarizes recent findings on additional molecular targets of STIM proteins including SERCA, IP3Rs, end-binding proteins (EB), presenilin, and CaMKII. Dysregulation of the SOCE-associated toolkit, including STIMs, contributes to the development of neurodegenerative disorders (e.g., Alzheimer's disease, Parkinson's disease, and Huntington's disease), traumatic brain injury, epilepsy, and stroke. Emerging evidence points to the role of STIM proteins and several of their molecular effectors and regulators in neuronal and glial physiology and pathology, suggesting their potential application for future therapeutic strategies.

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Regulation of Store-Operated Ca2+ Entry by Septins

Cited by 23 publications

References 61 publications

Distinct segregation patterns of yeast cell-peripheral proteins uncovered by a method for protein segregatome analysis

Distinct segregation patterns of yeast cell-peripheral proteins uncovered by a method for protein segregatome analysis

More Than Just Simple Interaction between STIM and Orai Proteins: CRAC Channel Function Enabled by a Network of Interactions with Regulatory Proteins

Target Molecules of STIM Proteins in the Central Nervous System

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