Association of annexin A5 with Na+/Ca2+ exchanger and caveolin-3 in non-failing and failing human heart

Camors, Emmanuel; Charue, Dominique; Trouvé, Pascal; Monceau, Virginie; Loyer, Xavier; Russo‐Marie, Françoise; Charlemagne, D.

doi:10.1016/j.yjmcc.2005.08.009

Cited by 36 publications

(32 citation statements)

References 41 publications

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“…The annexins are calcium-dependent membrane binding proteins found at the Z band or transverse tubules in heart and skeletal muscle (26). Annexin A6 is an atypical family member with eight instead of four annexin domains.…”

Section: Discussionmentioning

confidence: 99%

Annexin A6 modifies muscular dystrophy by mediating sarcolemmal repair

Swaggart¹,

Demonbreun²,

et al. 2014

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

123

159

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Many monogenic disorders, including the muscular dystrophies, display phenotypic variability despite the same disease-causing mutation. To identify genetic modifiers of muscular dystrophy and its associated cardiomyopathy, we used quantitative trait locus mapping and whole genome sequencing in a mouse model. This approach uncovered a modifier locus on chromosome 11 associated with sarcolemmal membrane damage and heart mass. Whole genome and RNA sequencing identified Anxa6, encoding annexin A6, as a modifier gene. A synonymous variant in exon 11 creates a cryptic splice donor, resulting in a truncated annexin A6 protein called ANXA6N32. Live cell imaging showed that annexin A6 orchestrates a repair zone and cap at the site of membrane disruption. In contrast, ANXA6N32 dramatically disrupted the annexin A6-rich cap and the associated repair zone, permitting membrane leak. Anxa6 is a modifier of muscular dystrophy and membrane repair after injury.dystrophin | muscle | plasma membrane

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Section: Discussionmentioning

confidence: 99%

Annexin A6 modifies muscular dystrophy by mediating sarcolemmal repair

Swaggart¹,

Demonbreun²,

et al. 2014

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

123

159

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“…Additionally, calcineurin, 14-3-3⑀ and F-actin have been shown to associate with the Na/Ca exchanger and modulate its activity (56 -58). Finally, both caveolin 3 and annexin A5 may also associate with Na/Ca exchanger in vivo (59,60). Although it is likely that one or more of these proteins may influence the cellular pathways responsible for the localization and stability of Na/Ca exchanger in cardiomyocytes, in vivo data to support the physiological relevance of these interactions is not yet available.…”

Section: Discussionmentioning

confidence: 99%

Targeting and Stability of Na/Ca Exchanger 1 in Cardiomyocytes Requires Direct Interaction with the Membrane Adaptor Ankyrin-B

Cunha

Bhasin

Mohler

2007

Journal of Biological Chemistry

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Na/Ca exchanger activity is important for calcium extrusion from the cardiomyocyte cytosol during repolarization. Animal models exhibiting altered Na/Ca exchanger expression display abnormal cardiac phenotypes. In humans, elevated Na/Ca exchanger expression/activity is linked with pathophysiological conditions including arrhythmia and heart failure. Whereas the molecular mechanisms underlying Na/Ca exchanger biophysical properties are widely studied and generally well characterized, the cellular pathways and molecular partners underlying the specialized membrane localization of Na/Ca exchanger in cardiac tissue are essentially unknown. In this report, we present the first direct evidence for a protein pathway required for Na/Ca exchanger localization and stability in primary cardiomyocytes. We define the minimal structural requirements on ankyrin-B for direct Na/Ca exchanger interactions. Moreover, using ankyrin-B mutants that lack Na/Ca exchanger binding activity, and primary cardiomyocytes with reduced ankyrin-B expression, we demonstrate that direct interaction with the membrane adaptor ankyrin-B is required for the localization and post-translational stability of Na/Ca exchanger 1 in neonatal mouse cardiomyocytes. These results raise exciting new questions regarding potentially dynamic roles for ankyrin proteins in the biogenesis and maintenance of specialized membrane domains in excitable cells.

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“…The clinical data of patients have been described previously (12). Briefly, patients presented increases in LV mass and decreased LV ejection fraction (14 Ϯ 5%).…”

Section: Srfmentioning

confidence: 99%

“…Because the increase in desmin-AGE was rather specific among the bands present on the blot, we hypothesized that human desmin, which is conserved from mouse to human, could also be targeted by AGE in human DCM. As a first step in identifying potential alterations of desmin in the context of human heart failure, we examined the pattern of AGE modification in samples of human hearts from patients presenting cardiac dilation (12). Sequential Western blot analysis with the anti-AGE antibody and anti-desmin antibody revealed an increased band with identical apparent M r as desmin in 6 of 7 patients (Fig.…”

Section: Figure 4 Age Formation On Desmin In Srf Hko Induced Dcm Andmentioning

confidence: 99%

Muscle Creatine Kinase Deficiency Triggers Both Actin Depolymerization and Desmin Disorganization by Advanced Glycation End Products in Dilated Cardiomyopathy

Diguet

Mallat

Ladouce

et al. 2011

Journal of Biological Chemistry

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Alterations in the balance of cytoskeleton as well as energetic proteins are involved in the cardiac remodeling occurring in dilated cardiomyopathy (DCM). We used two-dimensional DIGE proteomics as a discovery approach to identify key molecular changes taking place in a temporally controlled model of DCM triggered by cardiomyocyte-specific serum response factor (SRF) knock-out in mice. We identified muscle creatine kinase (MCK) as the primary down-regulated protein followed by ␣-actin and ␣-tropomyosin down-regulation leading to a decrease of polymerized F-actin. The early response to these defects was an increase in the amount of desmin intermediate filaments and phosphorylation of the ␣B-crystallin chaperone. We found that ␣B-crystallin and desmin progressively lose their striated pattern and accumulate at the intercalated disk and the sarcolemma, respectively. We further show that desmin is a preferential target of advanced glycation end products (AGE) in mouse and human DCM. Inhibition of CK in cultured cardiomyocytes is sufficient to recapitulate both the actin depolymerization defect and the modification of desmin by AGE. Treatment with either cytochalasin D or glyoxal, a cellular AGE, indicated that both actin depolymerization and AGE contribute to desmin disorganization. Heat shock-induced phosphorylation of ␣B-crystallin provides a transient protection of desmin against glyoxal in a p38 MAPK-dependent manner. Our results show that the strong down-regulation of MCK activity contributes to F-actin instability and induces post-translational modification of ␣B-crystallin and desmin. Our results suggest that AGE may play an important role in DCM because they alter the organization of desmin filaments that normally support stress response and mitochondrial functions in cardiomyocytes.

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Association of annexin A5 with Na+/Ca2+ exchanger and caveolin-3 in non-failing and failing human heart

Cited by 36 publications

References 41 publications

Annexin A6 modifies muscular dystrophy by mediating sarcolemmal repair

Annexin A6 modifies muscular dystrophy by mediating sarcolemmal repair

Targeting and Stability of Na/Ca Exchanger 1 in Cardiomyocytes Requires Direct Interaction with the Membrane Adaptor Ankyrin-B

Muscle Creatine Kinase Deficiency Triggers Both Actin Depolymerization and Desmin Disorganization by Advanced Glycation End Products in Dilated Cardiomyopathy

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