Stress & Citoesqueleto

Interesse da Investigação

Microtubules (Mts) are polarized polymers of α/β-tubulin heterodimers participating in a wide range of cell functions, e.g. cell division, cell signalling, intracellular transport and locomotion. How Mts accomplish this variety of functions is far from being completely understood. Although there is a increasing data concerning this subject, one of the most attractive questions in the field of tubulin/Mt biogenesis is still "how is the functional tubulin 3D-structure achieved in the cell?" and "how is this related with Mt biogenesis, function dynamics and recycling of tubulin heterodimers in vivo?" The maturation of tubulin heterodimers is a complex process involving the interaction of tubulins with several proteins: molecular chaperones (e.g. the cytosolic chaperonin containing TCP1- CCT) and the tubulin cofactors (TBCA-TBCE).
The main goal of the Stress and Cytoskeleton group is to understand how the components of the tubulin folding pathway control tubulin synthesis, flux, transport and heterodimers recycling and therefore are putative targets for regulation of the assembly of specialized Mt structures (i.e. cilia) and Mt dynamics.
Regarding the biological role of CCT, tubulin cofactors and related proteins research has been focused on studies of:
a) how tubulin cofactor E and CCT-subunits are involved in biogenesis and maintenance of cilia in the protozoa ciliate Tetrahymena.
b) how the knockdown of the TBCA gene perturbs the mammalian Mt cytoskeleton and its dynamics as well as in the investigation of how TBCA is able to respond to alterations of the native tubulin heterodimers pool.
c) the biological role of the recently described human Cofactor C related protein, TBCC-domain containing 1 (TBCCD1), which we propose to be a key regulator of centrosome positioning and consequently of internal cell organization.

We are also studing how Mt dynamics in mammalian cells is related to biophysical properties of these polymers, with the goal of establishing nano-devices where Mts and associated motor proteins are used as deliver target systems.
Finally, the group is investigating how rearrangements in the Mt cytoskeleton of the Apicomplexa protozoan parasite Besnoitia besnoiti that causes disease in bovine, are involved in the first steps of host cell invasion

Publicações

(Selected) Updated June (2010).

Seixas C, Cruto T, Tavares A, Gaertig J, Soares H. (2010). CCTalpha and CCTdelta chaperonin subunits are essential and required for cilia assembly and maintenance in Tetrahymena PLoS One 5(5) :e10704

Gonçalves, J, Nolasco,S, Nascimento, R, Lopez Fanarraga, M, Zabala, JC and Soares, H. (2010). TBCCD1, a new centrosomal protein is required for centrosome and Golgi apparatus positioning. EMBO Reports 11 :194-200

Ramalho, RR, Soares, H and Melo, LV (2007). Microtubule behavior under strong electromagnetic fields. Mat. Sci. Eng. C. 27 :1207–1210

Reis, Y, Cortes, H, Viseu Melo, L, Fazendeiro, I, Leitao, A and Soares, H. (2006). Microtubule cytoskeleton behavior in the initial steps of host cell invasion by Besnoitia besnoiti FEBS Lett 580 :4673-82

Nolasco S, Bellido J, Gonçalves J, Zabala JC and Soares, H. (2005). Tubulin cofactor A gene silencing in mammalian cells induces changes in microtubule cytoskeleton, cell cycle arrest and cell death FEBS Lett 579 :3515-3524

Seixas, C., Casalou, C., Melo, L.V., Nolasco, S., Brogueira, P. and Soares, H. (2003). Subunits of the chaperonin CCT are associated with Tetrahymena microtubule structures and are involved in cilia biogenesis. Exp. Cell Res. 290 :303-321

Domingues, C., Soares, H., Rodrigues-Pousada, C. and Cyrne, L. (1999). Structure of Tetrahymena CCTq gene and its expression under colchicine treatment. Bioch. Bioph. Acta. 1446 :443-449

Soares, H., Cyrne, L., Casalou, C., Ehmann, B. and Rodrigues-Pousada, C. (1997). The third member of Tetrahymena CCT-subunit gene family, TpCCTa, encodes a component of the hetero-oligomeric chaperonin complex. Biochem J., 326 :21-29

Soares, H., Penque, D., Mouta, C, and Rodrigues-Pousada, C. (1994). A Tetrahymena orthologue of the mouse chaperonin subunit CCTg and its co-expression with tubulin during cilia recovery. J. Biol. Chem. 269 :29299-29307

Dujon B, (...) Soares, H. (...) and Mewes HW (107 authors) (1994). Complete DNA sequence of yeast chromosome XI Nature 369 :371-378