Calcium-dependent Binding of Sorcin to the N-terminal Domain of Synexin (Annexin VII)

Brownawell, Amy M.; Creutz, Carl E.

doi:10.1074/jbc.272.35.22182

Cited by 89 publications

(79 citation statements)

References 42 publications

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“…This peptide provides a suitable model to monitor complex formation between the whole protein and sorcin, as indicated by the data of Brownawell and Creutz (9) and by the control experiments performed. Fig.…”

Section: Discussionmentioning

confidence: 99%

“…was used to obtain quantitative information on the interaction between sorcin and annexin VII, which is known to involve the N-terminal domains of both proteins (9,23).…”

Section: Interaction Of Wild-type Sorcin and Its Site-specific Mutantmentioning

confidence: 99%

“…All these proteins bind to cell membranes through a Ca 2ϩ -dependent interaction with protein targets that permits transduction of various Ca 2ϩ -mediated signals. Sorcin is thought to participate in different Ca 2ϩ -triggered biochemical cascades since different target proteins have been identified in the cell types where the protein is expressed constitutively, namely the ryanodine receptor (Ryr) and the ␣ 1 subunit of L-type calcium channels in muscle cells (6,7), presenilin 2 in human brain (8), and annexin VII in adrenal medulla (9), differentiating myocytes (10) and red blood cells (11).…”

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confidence: 99%

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Information Transfer in the Penta-EF-hand Protein Sorcin Does Not Operate via the Canonical Structural/Functional Pairing

Mella

Colotti

Zamparelli

et al. 2003

Journal of Biological Chemistry

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Sorcin is a typical penta-EF-hand protein that participates in Ca2؉ -regulated processes by translocating reversibly from cytosol to membranes, where it interacts with different target proteins in different tissues. Binding of two Ca 2؉ /monomer triggers translocation, although EF1, EF2, and EF3 are potentially able to bind calcium at micromolar concentrations. To identify the functional pair, the conserved bidentate -Z glutamate in these EF-hands was mutated to yield E53Q-, E94A-, and E124A-sorcin, respectively. Limited structural perturbations occur only in E124A-sorcin due to involvement of Glu-124 in a network of interactions that comprise the long D helix connecting EF3 to EF2. The overall affinity for Ca 2؉ and for two sorcin targets, annexin VII and the ryanodine receptor, follows the order wildtype > E53Q-> E94A-> E124A-sorcin, indicating that disruption of EF3 has the largest functional impact and that disruption of EF2 and EF1 has progressively smaller effects. Based on this experimental evidence, EF3 and EF2, which are not paired in the canonical manner, are the functional EF-hands. Sorcin is proposed to be activated upon Ca 2؉ binding to EF3 and transmission of the conformational change at Glu-124 via the D helix to EF2 and from there to EF1 via the canonical structural/functional pairing. This mechanism may be applicable to all penta-EF-hand proteins.

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Section: Discussionmentioning

confidence: 99%

“…was used to obtain quantitative information on the interaction between sorcin and annexin VII, which is known to involve the N-terminal domains of both proteins (9,23).…”

Section: Interaction Of Wild-type Sorcin and Its Site-specific Mutantmentioning

confidence: 99%

mentioning

confidence: 99%

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Information Transfer in the Penta-EF-hand Protein Sorcin Does Not Operate via the Canonical Structural/Functional Pairing

Mella

Colotti

Zamparelli

et al. 2003

Journal of Biological Chemistry

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“…Synexin, also known as annexin VII, is a member of the annexin family of calcium-and phospholipid-binding proteins (50). We then asked whether the protein sorcin, which has previously been shown to interact with the N-terminal region of synexin (47), might also interact with the PS2 loop. Sorcin is a member of the family of Ca 2ϩ -binding proteins harboring five EF-hand motifs (40,41).…”

Section: Identification Of Sorcin As An Interactor For the Large Hydrmentioning

confidence: 99%

Presenilin 2 Interacts with Sorcin, a Modulator of the Ryanodine Receptor

Pack-Chung¹,

Meyers²,

Pettingell³

et al. 2000

Journal of Biological Chemistry

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102

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Perturbed Ca2؉ homeostasis is a common molecular consequence of familial Alzheimer's disease-linked presenilin mutations. We report here the molecular interaction of the large hydrophilic loop region of presenilin 2 (PS2) with sorcin, a penta-EF-hand Ca 2؉ -binding protein that serves as a modulator of the ryanodine receptor intracellular Ca 2؉ channel. The association of endogenous sorcin and PS2 was demonstrated in cultured cells and human brain tissues. Membrane-associated sorcin and a subset of the functional PS2 complexes were co-localized to a novel subcellular fraction that is distinctively positive for calcineurin B. Sorcin was found to interact with PS2 endoproteolytic fragments but not full-length PS2, and the sorcin/PS2 interaction was greatly enhanced by treatment with the Ca 2؉ ionophore A23187. Our findings reveal a molecular link between PS2 and intracellular Ca 2؉ channels (i.e. ryanodine receptor) and substantiate normal and/or pathological roles of PS2 in intracellular Ca 2؉ homeostasis.Nearly half of early-onset familial Alzheimer's disease (FAD) 1 is associated with mutations in genes encoding two homologous proteins, presenilin 1 (PS1) and presenilin 2 (PS2) (1). Recent studies have shown that PS1 (and perhaps PS2) plays an essential role in the ␥-secretase cleavage of amyloid ␤-protein precursor (2-4) and the trafficking/maturation of other select cellular proteins, including Notch and TrkB (5-8). Common molecular consequences of presenilin FAD mutations include the increased production of amyloid ␤-peptide x-42 and increased apoptosis (reviewed in Refs. 9 -11). In addition, FAD mutations in both PS1 and PS2 have been shown to disrupt intracellular Ca 2ϩ homeostasis (12, 13). However, the mechanism by which Ca 2ϩ dyshomeostasis contributes to FAD pathogenesis is still unresolved.Recently, a number of molecules that form complexes with the presenilins have been identified, including ␤-and ␦-catenin (14 -19), p0071 (20), amyloid ␤-protein precursor (21), filamin/ Fh-1 (22), Notch (23), GSK3␤ (24), Rab11 (25), calsenilin (26), calmyrin (27), QM/Jif-1 (28), and Bcl-X L (29). It is currently unclear whether these interactions mediate pathogenesis in presenilin FAD. It is also noteworthy that some of these proteins have been shown to interact either preferentially or exclusively with full-length presenilin over the N-or C-terminal fragments. Since only a subset of presenilin proteins are cleaved to form stable, functional presenilin complexes (30 -35), and the remaining full-length proteins are degraded by the proteasome (32, 36 -38), proteins that interact with the Nand/or C-terminal presenilin fragments are more likely to mediate presenilin function as opposed to maturation of the presenilins. Additionally, many of these presenilin-interacting proteins have been identified and characterized using overexpression in cell systems, whereas only a few have been demonstrated to interact with PS1 and/or PS2 endogenously (e.g. ␤-catenin).Although the N-terminal and loop domains are not conserved betw...

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“…6b). First of all, ANXA7 binding partners, galectin-3, LGALS3 24 and sorcin, SRI 25 are directly linked to the AR-RB crosstalk. Galectin-3 was shown to affect RB1 profile 26,27 similar to ANXA7, implying that WT-ANXA7 could employ its binding partner for regulating RB1 expression and phosphorylation in prostate cancer cells.…”

Section: Anxa7 Protein Affected Cell Viability In Prostate Cancer Celmentioning

confidence: 99%

Annexin‐A7 protects normal prostate cells and induces distinct patterns of RB‐associated cytotoxicity in androgen‐sensitive and ‐resistant prostate cancer cells

Torosyan

Šimáková

Shanmugam

et al. 2009

Intl Journal of Cancer

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The tumor suppressor role of annexin-A7 (ANXA7) was previously demonstrated by cancer susceptibility in Anxa7(1/2)-mice and by ANXA7 loss in human cancers, especially in hormone-resistant prostate tumors. To gain mechanistic insights into ANXA7 tumor suppression, we undertook an in vitro study in which we compared wild-type (WT)-ANXA7 and dominant-negative (DN)-ANXA7 effects to a conventional tumor suppressor p53 in prostate cancer cells with different androgen sensitivity. Unlike p53 (which caused cell growth arrest and apoptosis to a noticeable extent in benign PrEC), WT-ANXA7 demonstrated profound cytotoxicity in androgen-sensitive LNCaP as well as in the androgen-resistant DU145 and PC3 prostate cancer cells, but not in PrEC. In androgen-sensitive LNCaP, WT-ANXA7 decreased lowmolecular-weight (LMW) AR protein forms and maintained higher retinoblastoma 1 (RB1)/phospho-RB1 ratio. In contrast, DN-ANXA7 (which lacks phosphatidylserine liposome aggregation properties) increased LMW-AR forms and hyperphosphorylated RB1 that was consistent with the lack of DN-ANXA7 cytotoxicity. According to the microarray-based Ingenuity Pathways Analysis, a major WT-ANXA7 effect in androgen-sensitive LNCaP constituted of upregulation of the RB1-binding transcription factor E2F1 along with its downstream proapoptotic targets such as ASK1 and ASPP2. These results suggested a reversal of the RBdependent repression of the proapoptotic E2F-mediated transcription. However, DN-ANXA7 increased RB1/2 (but not E2F1) expression and induced the proliferation-promoting ERK5, thereby maintaining the RB-dependent repression of E2F-mediated apoptosis in LNcaP. On the other hand, in androgen-resistant cells, WT-ANXA7 tumor suppressor effects involved PTEN and NFkB pathways. Thus, ANXA7 revived the RB-associated cell survival control and overcame androgen resistance and dysfunctional status of major tumor suppressors commonly mutated in prostate cancer. Published 2009 UICC. This article is a US Government work and, as such, is in the public domain in the United States of America.Key words: annexin-A7 vs. p53; RB-E2F; AR; prostate cancer; Ingenuity Pathways Analysis Annexin-VII (ANXA7 or synexin) is a ubiquitously expressed member of the multifunctional Ca/phospholipid-binding annexin family. In addition to Ca 21 -activated GTPase activity as well as involvement in membrane fusion and exocytosis, ANXA7 demonstrated tumor suppressor function in murine model 1 and in human prostate and breast cancers. 2,3 Our large-scale study on ANXA7 protein expression in different cancers 4 identified a drastic ANXA7 loss in the hormone-refractory prostate cancers as well as an abundant ANXA7 presence in the adrenal gland, a major source of sex hormone precursors. Although tumor suppressor mechanisms of ANXA7 are not yet elucidated, these data suggested that ANXA7, which has androgen-receptor (AR) regulatory elements in its promoter, may be involved in the regulation of androgen-dependent cell survival in prostate cancer cells.Androgen-dependent proliferation is p...

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Calcium-dependent Binding of Sorcin to the N-terminal Domain of Synexin (Annexin VII)

Cited by 89 publications

References 42 publications

Information Transfer in the Penta-EF-hand Protein Sorcin Does Not Operate via the Canonical Structural/Functional Pairing

Information Transfer in the Penta-EF-hand Protein Sorcin Does Not Operate via the Canonical Structural/Functional Pairing

Presenilin 2 Interacts with Sorcin, a Modulator of the Ryanodine Receptor

Annexin‐A7 protects normal prostate cells and induces distinct patterns of RB‐associated cytotoxicity in androgen‐sensitive and ‐resistant prostate cancer cells

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