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Actin depolymerization mediated loss of SNTA1 phosphorylation and Rac1 activity has implications on ROS production, cell migration and apoptosis

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Alpha-1-syntrophin (SNTA1) and Rac1 are part of a signaling pathway via the dystrophin glycoprotein complex (DGC). Both SNTA1 and Rac1 proteins are over-expressed in various carcinomas. It is through the DGC signaling pathway that SNTA1 has been shown to act as a link between the extra cellular matrix, the internal cell signaling apparatus and the actin cytoskeleton. SNTA1 is involved in the modulation of the actin cytoskeleton and actin reorganization. Rac1 also controls actin cytoskeletal organization in the cell. In this study, we present the interplay between f-actin, SNTA1 and Rac1. We analyzed the effect of actin depolymerization on SNTA1 tyrosine phosphorylation and Rac1 activity using actin depolymerizing drugs, cytochalasin D and latrunculin A. Our results indicate a marked decrease in the tyrosine phosphorylation of SNTA1 upon actin depolymerization. Results suggest that actin depolymerization mediated loss of SNTA1 phosphorylation leads to loss of interaction between SNTA1 and Rac1, with a concomitant loss of Rac1 activation. The loss of SNTA1tyrosine phosphorylation and Rac1 activity by actin depolymerization results in increased apoptosis, decreased cell migration and decreased reactive oxygen species (ROS) levels in breast carcinoma cells. Collectively, our results present a possible role of f-actin in the SNTA1-Rac1 signaling pathway and implications of actin depolymerization on cell migration, ROS production and apoptosis.

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Acknowledgments

This work was supported by Deanship of Research, King Fahd University of Petroleum and Minerals, through the start-up grant scheme to Dr. Firdous A. Khanday, No. SR141006. It was partly financed by a grant to SSB by the University Grants Commission of India, No F. 17-82/2008(SA-I) to SSB. We are grateful to Dr. KS Siddiqui and A Ismail, for carrying out the scientific content and language editing of the manuscript.

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  1. Department of Biotechnology, University of Kashmir, Srinagar, Jammu and Kashmir, 190006, India

    Sehar Saleem Bhat, Arif Ali Parray, Umar Mushtaq, Khalid Majid Fazili & Firdous Ahmad Khanday

  2. Department of Life Sciences, King Fahd University of Petroleum and Minerals, Bld.: 7, Room: 129, Dhahran, 31261, Kingdom of Saudi Arabia

    Firdous Ahmad Khanday

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  1. Sehar Saleem Bhat
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Bhat, S.S., Parray, A.A., Mushtaq, U. et al. Actin depolymerization mediated loss of SNTA1 phosphorylation and Rac1 activity has implications on ROS production, cell migration and apoptosis. Apoptosis 21, 737–748 (2016). https://doi.org/10.1007/s10495-016-1241-6

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