Functional interaction between TRPC1 channel and connexin-43 protein: a novel pathway underlying S1P action on skeletal myogenesis

Meacci, Elisabetta; Bini, Francesca; Sassoli, Chiara; Martinesi, Maria; Squecco, Roberta; Chellini, Flaminia; Zecchi‐Orlandini, Sandra; Francini, Fabio; Formigli, Lucia

doi:10.1007/s00018-010-0442-3

Cited by 46 publications

(33 citation statements)

References 59 publications

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“…Similarly, S1P has also been proposed to play an important role in trafficking of non-malignant cells such as hematopoietic stem progenitor cells (6, 44), mesenchymal stromal cells (45), and endothelial progenitors (17). It thus plays a role in skeletal muscle development (46), angiogenesis (47), and tissue regeneration from injury (9) and acts directly on skeletal muscle satellite stem cells (26). …”

Section: Discussionmentioning

confidence: 99%

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Bioactive Lipids S1P and C1P Are Prometastatic Factors in Human Rhabdomyosarcoma, and Their Tissue Levels Increase in Response to Radio/Chemotherapy

Schneider

Bryndza

Abdel‐Latif

et al. 2013

Molecular Cancer Research

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We observed that sphingosine-1-phosphate (S1P) and ceramide-1-phosphate (C1P) strongly enhance in vitro motility and adhesion of human rhabdomyosarcoma (RMS) cells. This effect was observed at physiological concentrations of both bioactive lipids, which are present in biological fluids, and is much stronger than the effects observed in response to known RMS pro-metastatic factors such as stromal derived factors-1 (SDF-1) or hepatocyte growth factor/scatter factor (HGF/SF). We also present novel evidence that the levels of S1P and C1P increase in several organs after γ-irradiation or chemotherapy, which indicates induction of an unwanted pro-metastatic environment related to treatment. Most importantly, we found that the metastasis of RMS cells in response to S1P can be effectively inhibited in vivo with the S1P-specific binder NOX-S93 that is based on a high affinity Spiegelmer. We propose that bioactive lipids play a previously underappreciated role in dissemination of RMS and the unwanted side effects of radio/chemotherapy by creating a pro-metastatic microenvironment. Therefore, an anti-metastatic treatment with specific S1P-binding scavenger such as NOX-S93 could become a part of standard radio/chemotherapy.

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Section: Discussionmentioning

confidence: 99%

“…The effects of S1P and C1P in myogenesis (8, 46) could be relevant to the effect on RMS proliferation. However, we did not observe any effect of either bioactive lipid on proliferation or survival of RMS cells.…”

Section: Discussionmentioning

confidence: 99%

Bioactive Lipids S1P and C1P Are Prometastatic Factors in Human Rhabdomyosarcoma, and Their Tissue Levels Increase in Response to Radio/Chemotherapy

Schneider

Bryndza

Abdel‐Latif

et al. 2013

Molecular Cancer Research

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“…Focal adhesions act as multi-protein signaling complexes as well as having the structural role of linking membrane receptors and the actin cytoskeleton. Gap junctions are an important component of intercalated discs in cardiac muscle [43] and are necessary for skeletal muscle differentiation [44]. Tight junctions, also known as zonula occludens, are important for signaling [45].…”

Section: Discussionmentioning

confidence: 99%

Multi-Tasking Role of the Mechanosensing Protein Ankrd2 in the Signaling Network of Striated Muscle

et al. 2011

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BackgroundAnkrd2 (also known as Arpp) together with Ankrd1/CARP and DARP are members of the MARP mechanosensing proteins that form a complex with titin (N2A)/calpain 3 protease/myopalladin. In muscle, Ankrd2 is located in the I-band of the sarcomere and moves to the nucleus of adjacent myofibers on muscle injury. In myoblasts it is predominantly in the nucleus and on differentiation shifts from the nucleus to the cytoplasm. In agreement with its role as a sensor it interacts both with sarcomeric proteins and transcription factors.Methodology/Principal FindingsExpression profiling of endogenous Ankrd2 silenced in human myotubes was undertaken to elucidate its role as an intermediary in cell signaling pathways. Silencing Ankrd2 expression altered the expression of genes involved in both intercellular communication (cytokine-cytokine receptor interaction, endocytosis, focal adhesion, tight junction, gap junction and regulation of the actin cytoskeleton) and intracellular communication (calcium, insulin, MAPK, p53, TGF-β and Wnt signaling). The significance of Ankrd2 in cell signaling was strengthened by the fact that we were able to show for the first time that Nkx2.5 and p53 are upstream effectors of the Ankrd2 gene and that Ankrd1/CARP, another MARP member, can modulate the transcriptional ability of MyoD on the Ankrd2 promoter. Another novel finding was the interaction between Ankrd2 and proteins with PDZ and SH3 domains, further supporting its role in signaling. It is noteworthy that we demonstrated that transcription factors PAX6, LHX2, NFIL3 and MECP2, were able to bind both the Ankrd2 protein and its promoter indicating the presence of a regulatory feedback loop mechanism.Conclusions/SignificanceIn conclusion we demonstrate that Ankrd2 is a potent regulator in muscle cells affecting a multitude of pathways and processes.

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“…Signaling pathways leading to TRPC activation is still a debated issue, but it was shown that TRPC1, TRPC4 and TRPC5 participate to SOCE in several cell types (Ambudkar, 2007;Worley et al, 2007;Yuan et al, 2007;Salido et al, 2011), including primary mouse myotubes and C2C12 mouse muscle cell line (Vandebrouck et al, 2007;Louis et al, 2008;Sabourin et al, 2009). In addition, TRPC1 was shown to play an important role to sustain skeletal muscle contraction (Zanou et al, 2010) and, in C2C12 cell line, TRPC1 silencing decreased SOCE and the fusion process (Louis et al, 2008;Formigli et al, 2009;Meacci et al, 2010), hence impairing muscle formation. Another study reported a role of TRPC3 in myogenesis, but using cells that also lack the dihydropyridine receptor (Woo et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

During post-natal human myogenesis, normal myotube size requires TRPC1 and TRPC4 mediated Ca2+ entry

Antigny¹,

Koenig²,

Bernheim³

et al. 2013

Journal of Cell Science

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SummaryMyogenesis involves expression of muscle-specific transcription factors such as myogenin and myocyte enhancer factor 2 (MEF2), and is essentially regulated by fluctuations of cytosolic Ca 2+ concentration. Recently we demonstrated that molecular players of storeoperated Ca 2+ entry (SOCE), stromal interacting molecule (STIM) and Orai, were fundamental in the differentiation process of postnatal human myoblasts. Besides STIM and Orai proteins, the family of transient receptor potential canonical (TRPC) channels was shown to be part of SOCE in several cellular systems. In the present study, we investigated the role of TRPC channels in the human myogenesis process. We demonstrate, using an siRNA strategy or dominant negative TRPC overexpression, that TRPC1 and TRPC4 participate in SOCE, are necessary for MEF2 expression, and allow the fusion process to generate myotubes of normal size. Conversely, the overexpression of STIM1 with TRPC4 or TRPC1 increased SOCE, accelerated myoblast fusion, and produced hypertrophic myotubes. Interestingly, in cells depleted of TRPC1 or TRPC4, the normalization of SOCE by increasing the extracellular calcium concentration or by overexpressing STIM1 or Orai1 was not sufficient to restore normal fusion process. A normal differentiation occurred only when TRPC channel was re-expressed. These findings indicate that Ca 2+ entry mediated specifically by TRPC1 and TRPC4 allow the formation of normal-sized myotubes.

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Functional interaction between TRPC1 channel and connexin-43 protein: a novel pathway underlying S1P action on skeletal myogenesis

Cited by 46 publications

References 59 publications

Bioactive Lipids S1P and C1P Are Prometastatic Factors in Human Rhabdomyosarcoma, and Their Tissue Levels Increase in Response to Radio/Chemotherapy

Bioactive Lipids S1P and C1P Are Prometastatic Factors in Human Rhabdomyosarcoma, and Their Tissue Levels Increase in Response to Radio/Chemotherapy

Multi-Tasking Role of the Mechanosensing Protein Ankrd2 in the Signaling Network of Striated Muscle

During post-natal human myogenesis, normal myotube size requires TRPC1 and TRPC4 mediated Ca2+ entry

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