Thursday, 14th December 2017
Cell Biology and Immunology
           Cell Polarity





 Miguel Alonso Grupo



Miguel Ángel Alonso




Research summary:

Cell polarity is fundamental to the functioning of most types of cell. Our group's aim is to advance our knowledge of the cell polarization process through the functional characterization of protein machinery involved in the generation and maintenance of cell polarization. Hepatocytes, T lymphocytes and epithelial cells are our preferred model cell systems. Special emphasis is placed on the functional characterization of the specialized transport pathways mediated by members of the MAL protein family and associated proteins in these cell types.


The primary cilium is a single appendage that projects from the cell surface of most vertebrate cells. One of the main features of primary cilia is that, unlike the motile cilia of multiciliary cells or of cells that use cilia or flagella for movement, they are non-motile. Important signaling pathways involved in cell proliferation, differentiation, survival and migration, such as Hedgehog, Wnt, Notch, signaling, are orchestrated in the primary cilium. Dysfunction of the cilium is associated with a long list of human developmental and degenerative disorders, collectively referred to as ciliopathies, that affect nearly every major body organ.


Our group has recently discovered that the remnant of the midbody, also known as the Flemming body, a structure that forms in the middle of the intercellular bridge during cytokinesis, plays an essential role in this process. In polarized epithelial cells, once the intercellular bridge is cleaved at one site, the midbody is inherited as a remnant by one of the daughter cells. The remnant moves along the apical membrane from a peripheral to a central position, where the centrosome has already docked. Once the two structures have met, the midbody enables the centrosome to form a primary cilium by a mechanism that is currently being investigated in our laboratory. In addition to developing a new model of primary cilium biogenesis, our work has established a functional connection between the three main microtubule-based cell compartments: the centrosome, the midbody and the primary cilium.

 Fig2 New Web

Figure 1. The midbody remnant enables the centrosome for primary cilium formation. (A) The images correspond to3D reconstructions of cells stably expressing cherry-tubulin that were filmed during cell division.The images were pseudocolored based on height using the color scale on the left to highlight that the intracellular bridge forms at the top of the cells and that the post-mitotic midbody remnant localizes after abcission at a peripheral position at the apical surface. The arrowhead points to the post-mitotic midbody. An enlargement of the boxed region at 0 min and 80 min is also shown. (B) Three-dimensional reconstruction of images obtained by videomicroscopic analysis of cells expressing GFP-tubulin (midbody remnant and primary cilium) and dsRed-centrin (centrosome) during the movement of the midbody to encounter the centrosome for primary cilium formation. The green and red arrowheads point to the midbody remnant and the centrosome, respectively.


Relevant publications (2012-2017):

- 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.

- Rodríguez-Fraticelli, A. E., Auzan, M., Alonso, M.A., Bornens, B., and Martín-Belmonte, F. (2012) Cell-confinement controls epithelial polarity and lumen formation through cortical actin contractility and LKB1 in micropatterned MDCK 3D-cultures. J. Cell Biol. 198, 1011-1023.

-Soares, H., Henriques, R., Sachse, M., Ventimiglia, Zimmer, C., Tholouze, M-I, Alonso, M.A., Schwartz, O., Thoulouze, M.-I., and Alcover, A. (2013) Regulated vesicle fusion generates signaling nanoterritories that control T cell activation at the immunological synapse. J. Exp. Med. 210, 2414-2433.

- Andrés-Delgado, L., Antón, O.M., and Alonso, M.A. (2013) Centrosome polarization in T cells: a task for formins. Front. Immunol. 4, 191.

- Ventimiglia, L.N., and Alonso, M.A. (2013) The role of membrane rafts in Lck transport, regulation and signalling in T-cells. Biochem J. 454, 169-79.

- 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.

- Rodríguez-Fraticelli, A.E., Bagwell, J., Bosch-Fortea, M., Boncompain, G., Reglero, N., García-León, M.J., Andrés, G., Toribio, M.L., Alonso, M.A., Millan, J., Perez, F., Bagnat, M., and Martín-Belmonte, F. (2015) Developmental regulation of apical endocytosis controls epithelial patterning in vertebrate tubular organs. Nat. Cell Biol.17, 241-250.

- Reales,E., Bernabé-Rubio, M.,Casares-Arias,J.,Rentero, C., Fernández-Barrera, J., Rangel, L., Correas, I., Enrich, C., Andrés, G. and Alonso, M.A.(2015) The MAL protein is crucial for proper membrane condensation at the ciliary base, which is required for primary cilium elongation. J. Cell Sci. 128, 2261-2270.

- Rumah, K.R., MA, Y., Linden, J.R., Lin Oo, M., Anrather, J., Schaeren-Wiemers, N., Alonso, M.A., Fischetti, V.A., McClain, M.S., and Vartanian, T. (2015) The Myelin and Lymphocyte protein MAL is required for binding and activity of Clostridium perfringens e-toxin. PLoS Pathog. 11: e1004896. doi:10.1371/journal.ppat.1004896

- Ventimiglia, L.N., Fernández-Martín,L.,Martínez-Alonso, M., Antón, O.M., Guerra, M., Martínez-Menárguez, J.A., Andrés, G., and Alonso, M.A. (2015) Regulation of exosome secretion by the integral MAL protein in T cells. J. Immunol. 195, 810-814.

- Marcos-Ramiro, B., García-Weber, D., Barroso, S., Feito, J., Ortega, M.C., Cernuda-Morollón, E., Reglero-Real, N., Fernández-Martín, L., Durán, M.C., Alonso, M.A., Correas, I., Cox, S., Ridley, A.J. and Millán, J. (2016) RhoB controls endothelial barrier recovery by inhibiting Rac1 trafficking to the cell border. J. Cell Biol. 213, 385-402.

- Ventimiglia, L.N. and Alonso, M.A. (2016) Biogenesis and function of T cell-derived exosomes. Front. Cell Dev. Biol. 4, 84. doi: 10.3389/fcell.2016.00084

-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.

- Bernabé-Rubio, M., and Alonso, M.A. (2017) Routes and machinery of primary cilium biogenesis. Cell. Mol. Life Sci. doi: 10.1007/s00018-017-2570-5


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