Cardiac striatin interacts with caveolin-3 and calmodulin in a calcium sensitive manner and regulates cardiomyocyte spontaneous contraction rate

Nader, Moni; Alotaibi, Shahd; Alsolme, Ebtehal; Khalil, Bariaa; Abu‐Zaid, Ahmed; Alsomali, Rahmah; Bakheet, Dana; Dzimiri, Nduna

doi:10.1139/cjpp-2017-0155

Cited by 12 publications

(6 citation statements)

References 42 publications

(34 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…elegans , members of the complex control polarity establishment during embryogenesis [33]. In humans, STRIPAK complex governs embryonic stem cell differentiation, proper cardiac function, dendritic spine morphology and cancer [34, 35].…”

Section: Discussionmentioning

confidence: 99%

Assembly of a heptameric STRIPAK complex is required for coordination of light-dependent multicellular fungal development with secondary metabolism in Aspergillus nidulans

et al. 2019

View full text Add to dashboard Cite

Eukaryotic striatin forms striatin-interacting phosphatase and kinase (STRIPAK) complexes that control many cellular processes including development, cellular transport, signal transduction, stem cell differentiation and cardiac functions. However, detailed knowledge of complex assembly and its roles in stress responses are currently poorly understood. Here, we discovered six striatin (StrA) interacting proteins (Sips), which form a heptameric complex in the filamentous fungus Aspergillus nidulans . The complex consists of the striatin scaffold StrA, the Mob3-type kinase coactivator SipA, the SIKE-like protein SipB, the STRIP1/2 homolog SipC, the SLMAP-related protein SipD and the catalytic and regulatory phosphatase 2A subunits SipE (PpgA), and SipF, respectively. Single and double deletions of the complex components result in loss of multicellular light-dependent fungal development, secondary metabolite production (e.g. mycotoxin Sterigmatocystin) and reduced stress responses. sipA (Mob3) deletion is epistatic to strA deletion by supressing all the defects caused by the lack of striatin. The STRIPAK complex, which is established during vegetative growth and maintained during the early hours of light and dark development, is mainly formed on the nuclear envelope in the presence of the scaffold StrA. The loss of the scaffold revealed three STRIPAK subcomplexes: (I) SipA only interacts with StrA, (II) SipB-SipD is found as a heterodimer, (III) SipC, SipE and SipF exist as a heterotrimeric complex. The STRIPAK complex is required for proper expression of the heterotrimeric VeA-VelB-LaeA complex which coordinates fungal development and secondary metabolism. Furthermore, the STRIPAK complex modulates two important MAPK pathways by promoting phosphorylation of MpkB and restricting nuclear shuttling of MpkC in the absence of stress conditions. SipB in A . nidulans is similar to human suppressor of IKK-ε(SIKE) protein which supresses antiviral responses in mammals, while velvet family proteins show strong similarity to mammalian proinflammatory NF-KB proteins. The presence of these proteins in A . nidulans further strengthens the hypothesis that mammals and fungi use similar proteins for their immune response and secondary metabolite production, respectively.

show abstract

Section: Discussionmentioning

confidence: 99%

Assembly of a heptameric STRIPAK complex is required for coordination of light-dependent multicellular fungal development with secondary metabolism in Aspergillus nidulans

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Protein extraction from cultured cells and Western blot analysis were performed as previously described [ 11 ]. The antibodies used were against STRN (BD Biosciences, cat #610838), α-tubulin (Sigma, cat #T9026), cytochrome C (Abcam, cat #ab13575), PARP (Cell Signaling, cat #9542L), cleaved caspase 3 (Cell Signaling, cat #9664L), GAPDH (Santa Cruz, cat # SC-25778) or actin (Santa Cruz, cat # SC-8432).…”

Section: Methodsmentioning

confidence: 99%

“…Similarly, silencing the STRN-4 gene induces apoptosis in KP4, PK9 and HCT116 cells [ 10 ]. Not only does STRN share high structural similarities with STRN-3 and -4, but it also contains binding domains to molecules (Calmodulin, caveolin-1 and -3, as well as PP2A) that are implicated in regulating apoptosis [ 4 , 11 , 12 , 13 , 14 , 15 ]. Nonetheless, STRN interacts with the oncosuppressor Adenomatous Polyposis Coli (APC) which is a substrate for caspases in apoptotic cells [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Striatin translocates to the cytosol of apoptotic cells and is proteolytically cleaved in a caspase 3-dependent manner

Nader

Khalil

Kattuah

et al. 2020

Heliyon

Self Cite

View full text Add to dashboard Cite

Striatin (STRN) is a multivalent protein holding great therapeutic potentials in view of its interaction with dynamic partners implicated in apoptosis. Although striatin-3 and striatin-4, that share high structural similarities with STRN, have been linked to apoptosis, the dynamics of STRN in apoptotic cells remain unclear. Herein, we report that the amount of STRN (110 kDa) is reduced in apoptotic cells, in response to various chemotherapeutic agents, thereby yielding a major polypeptide fragment at ~65 kDa, and three minor products at lower molecular weights. While STRN siRNA reduced the 65 kDa derivative fragment, the overexpression of a Myc-tagged STRN precipitated a novel fragment that was detected slightly higher than 65 kDa (due to the Myc-DDK tag on the cleaved fragment), confirming the cleavage of STRN during apoptosis. Interestingly, STRN cleavage was abrogated by the general caspase inhibitor Z-VAD.fmk. Cell fractionation revealed that the STRN pool, mainly distributed in the non-cytosolic fragment of naïve cells, translocates to the cytosol where it is proteolytically cleaved during apoptosis. Interestingly, the ectopic expression of caspase 3 in MCF-7 cells (deprived of caspase 3) induced STRN cleavage under apoptotic conditions. Inhibition of caspase 3 (Ac-DEVD-CHO) conferred a dose-dependent protection against the proteolytic cleavage of STRN. Collectively, our data provide cogent proofs that STRN translocates to the cytosol where it undergoes proteolytic cleavage in a caspase 3-dependent manner during apoptosis. Thus, this study projects the cleavage of STRN as a novel marker for apoptosis to serve pharmacological strategies targeting this particular form of cell death.

show abstract

“…The association at SNP rs2245109 is likely linked to gene STRN, in chromosome 2. This gene codes for protein striatin, which is expressed in cardiomyocytes and it has been shown to interact with other proteins implicated in the mechanism of myocardial function [24]. Moreover, mutations in this gene have been shown to lead to DCM in dogs.…”

Section: Genetic Findingsmentioning

confidence: 99%

Unsupervised ensemble-based phenotyping helps enhance the discoverability of genes related to heart morphology

Bonazzola¹,

Ferrante²,

Ravikumar³

et al. 2023

Preprint

View full text Add to dashboard Cite

Recent genome-wide association studies (GWAS) have been successful in identifying associations between genetic variants and simple cardiac parameters derived from cardiac magnetic resonance (CMR) images. However, the emergence of big databases including genetic data linked to CMR, facilitates investigation of more nuanced patterns of shape variability. Here, we propose a new framework for gene discovery entitled Unsupervised Phenotype Ensembles (UPE). UPE builds a redundant yet highly expressive representation by pooling a set of phenotypes learned in an unsupervised manner, using deep learning models trained with different hyperparameters. These phenotypes are then analyzed via (GWAS), retaining only highly confident and stable associations across the ensemble. We apply our approach to the UK Biobank database to extract left-ventricular (LV) geometric features from image-derived three-dimensional meshes. We demonstrate that our approach greatly improves the discoverability of genes influencing LV shape, identifying 11 loci with study-wide significance and 8 with suggestive significance. We argue that our approach would enable more extensive discovery of gene associations with image-derived phenotypes for other organs or image modalities.

show abstract

Cardiac striatin interacts with caveolin-3 and calmodulin in a calcium sensitive manner and regulates cardiomyocyte spontaneous contraction rate

Cited by 12 publications

References 42 publications

Assembly of a heptameric STRIPAK complex is required for coordination of light-dependent multicellular fungal development with secondary metabolism in Aspergillus nidulans

Assembly of a heptameric STRIPAK complex is required for coordination of light-dependent multicellular fungal development with secondary metabolism in Aspergillus nidulans

Striatin translocates to the cytosol of apoptotic cells and is proteolytically cleaved in a caspase 3-dependent manner

Unsupervised ensemble-based phenotyping helps enhance the discoverability of genes related to heart morphology

Contact Info

Product

Resources

About