CENTRO DE BIOLOGÍA MOLECULAR SEVERO OCHOACaptura de pantalla 2022 09 14 a las 10.27.10    

Cytoskeleton-plasma membrane interactions

Research summary:

Cell morphology and tissue organization are maintained through multiple interactions between lipids and proteins from the plasma membrane and the underlying cytoskeleton. The coordination between surface membranes and different cytoskeletal networks is essential for processes such as cell migration, polarity, epithelial and endothelial barrier stability, cell division or intracellular vesicular traffic. We are interested in investigating the role of proteins that regulate plasma membrane and/or cytoskeletal organization in different cellular processes. We have focused our attention on the 4.1 family of proteins 4.1R, 4.1B, 4.N y 4.1G—, which connect subcortical cytoskeleton to lipids and membranes through FERM (four-point-one, ezrin, radixin, moesin) domains. We are investigating the role of proteins 4.1 in cell migration, cell division and inflammation. A second aim of our group is to decipher the mechanisms involved in the generation of proteins 4.1 diversity as our data indicate that alternative splicing is not the only mechanism involved. In a collaborative basis, we are carrying out new studies focused on understanding the mechanisms and proteins involved in the formation of the primay cilium and the maintenance of endotelial barriers.

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The figure shows examples of different cellular localizations of protein 4.1.

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Relevant publications:

  • Rangel, L., Bernabé-Rubio, Fernández-Barrera, J, Casares-Arias, J., Millan, J., Alonso, M.A., and Correas, I. (2019) Caveolin-1a regulates primary cilium length by controling RhoA GTPase activity. Sci. Rep. 9, 1116.
  • Fernández-Barrera, J., Bernabé-Rubio, M., Casares-Arias, J., Rangel, L., Fernández-Martín, L., Correas, I., and Alonso, M.A. (2018) The actin-MRTF-SRF transcriptional circuit controls tubulin acetylation via a-TAT1 gene expression. J. Cell. Biol. 217:929-944.
  • Rangel L, Lospitao E, Ruiz-Sáenz A, Alonso MA, Correas I. (2017). Alternative polyadenylation in a family of paralogous EPB41 genes generates protein 4.1 diversity. RNA Biol. 14:236-244.
  • Bernabé-Rubio, M., Andrés, G., Casares-Arias, J., Fernández, J.J., Fernández-Barrera, J., Rangel, L., Reglero-Real, N., Gershlick, D.C., Fernández, J.J., Millán, J., Correas, I., Miguez, D.G., and Alonso, M.A. (2016) Novel role for the midbody in primary ciliogenesis by polarized epithelial cells. J. Cell Biol. 214, 259-273.
  • Marcos-Ramiro B, García-Weber D, Barroso S, Feito J, Ortega MC, Cernuda-Morollón E, Reglero-Real N, Fernández-Martín L, Durán MC, Alonso MA,Correas I, Cox S, Ridley AJ, Millán J (2016). RhoB controls endotelial barrier recovery by inhibiting Rac1 trafficking to the cell border. J Cell Biol. 213:385-402.
  • Reglero-Real, N., Alvarez-Varela, A., Cernuda-Morollón, E., Feito, J., Marcos-Ramiro, B., Fernández-Martín, L., Gómez-Lechón, M.J., Muntané, J., Sandoval, P., Majano, P.L., Correas, I., Alonso, M.A.,  and Millán, J. (2014) Apicobasal polarity controls lymphocyte adhesion to hepatic epithelial cells. Cell Rep. 8, 1879-93.
  • Ruiz-Saenz, A., van Haren, J., Sayas, C.L., Rangel, L., Demmers, J., Millán, J., Alonso, M.A., Galjart, N., and Correas, I. (2013) Protein 4.1R binds to CLASP2 and regulates dynamics, organization and attachment of microtubules to the cell cortex. J. Cell Sci. 126, 4589-601.
  • Andres-Delgado, L., Anton, O. M., Bartolini, F., Ruíz-Saénz, A, Correas, I., Gundersen, G. G., and Alonso, M. A. (2012) INF2 promotes the formation of detyrosinated microtubules necessary for reorientation of the centrosome to the immunological synapse of T cells. J. Cell Biol. 198, 1025-1037
  • Fernández-Martín L., Marcos-Ramiro B, Bigarella CL, Graupera, M, Cain RJ, Reglero-Real N, Jiménez A, Cernuda-Morollón E, Correas I, Cox S, Ridley AJ, Millán J. (2012). Crosstalk between reticular adherens junctions and platelet endothelial cell adhesion molecule-1 regulates endothelial barrier function. Arterioscler Thromb Vasc Biol. 32(8):e90-102.
  • Ruiz-Saenz, A., Kremer, L., Alonso, M. A., Millan, J., and Correas, I. (2011) Protein 4.1R regulates cell migration and IQGAP1 recruitment to the leading edge. J. Cell Sci. 124, 2529-2538.

Doctoral theses:

  • Laura Rangel Sánchez (2018). Regulación de la longitud del cilio primario por la proteína Caveolina 1. Universidad Autónoma de Madrid. Directores: Isabel Correas Hornero, Miguel Angel Alonso Lebrero.
  • Ana Ruiz Sáenz (2011). La proteína 4.1R regula la organización del citoesqueleto de tubulina y la migración celular. Universidad Autónoma de Madrid. Director: Isabel Correas.

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