Laboratory of Actin Cytoskeleton Regulation

1. The highly dynamic actin cytoskeleton is one of the structurally and functionally most important cellular constituents. The actin cytoskeleton is involved in such fundamental cell biological processes as the maintenance of cell shape, cell division, intracellular transport, and motility. Cytoskeleton regulation involves the concerted action of a few hundred proteins. Of these, our research group mainly focuses on functional characterization of the formin type of proteins by studying their cellular and molecular mechanisms. Coordinated regulation of the actin and microtubule cytoskeleton is known to play a pivotal role in the growth and proper navigation of neuronal axons and dendrites that are necessary to the formation of a functional nervous system. One of our major scientific interests is to gain a better understanding of the cytoskeletal mechanisms of axonal growth and guidance by uncovering the role of formins that appear to play key roles in both actin and microtubule remodeling. Besides neuronal cytoskeleton regulation, we use videomicroscopic approaches to investigate how formins contribute to cell shape changes and morphogenetic cell movements in the developing Drosophila compound eye and embryonic epidermis.

2. In addition, we are interested in the mechanisms of myofibrillogenesis. Myofibrils are composed of repeated sarcomeres that are extremely highly ordered macromolecular assemblies where structural organization is intimately linked to their functionality as contractile units. Recently, we developed a powerful nanoscopic approach that allowed us to determine the position of 27 muscle proteins with a quasi-molecular localization precision, and by means of template based protein structure modelling, we assembled a refined I-band and H-zone model with an unparalleled scope and resolution. We aim to combine this method with genetic approaches to explore the molecular mechanisms of sarcomere assembly during muscle development.

Our studies are of potential biomedical relevance as they may help to develop more efficient neuronal regeneration methods, and to understand sarcomere assembly and function in healthy and disease conditions.

Selected publications

Szikora, S., Gajdos, T., Novák, T., Farkas, D., Földi, I., Lenart, P., Erdélyi, M., Mihály, J. Nanoscopy reveals the layered organization of the sarcomeric H-zone and I-band complexes. J Cell Biol. 219(1): e201907026 (2020)

Migh E, Götz T, Földi I, Szikora S, Gombos R, Darula Z, Medzihradszky KF, Maléth J, Hegyi P, Sigrist S, Mihály J. Microtubule organization in presynaptic boutons relies on the formin DAAM. DEVELOPMENT 145 : 6 Paper: dev158519 , 13 p. (2018)

Szikora, S., Földi, I., Tóth, K., Migh, E., Vig, A., Bugyi, B., Maléth, J., Hegyi, P., Kaltenecker, P., Sanchez-Soriano, N., Mihály, J. The formin DAAM is required for coordination of the actin and microtubule cytoskeleton in axonal growth cones. J Cell Sci. 130(15):2506-2519. (2017)

Gombos, R ; Migh, E ; Antal, O ; Mukherjee, A ; Jenny, A ; Mihaly, J. The Formin DAAM Functions as Molecular Effector of the Planar Cell Polarity Pathway during Axonal Development in Drosophila. JOURNAL OF NEUROSCIENCE 35 : 28 pp. 10154-10167. , 14 p. (2015)

Molnár I, Migh E, Szikora S, Kalmár T, Végh AG, Deák F, Barkó S, Bugyi B, Orfanos Z, Kovács J, Juhász G, Váró G, Nyitrai M, Sparrow JC and Mihály J. DAAM is required for thin filament formation and sarcomerogenesis during muscle development in Drosophila. PLoS Genetics 10(2): e1004166 (2014)