The main interest of our team lies in understanding the regulation, organization and dynamics of acto-myosin contractile networks. We are particularly interested in the contractile ring that functions during cytokinesis to partition the contents of the mother cell into the two daughter cells.
During cytokinesis a contractile ring assembles around the cell equator beneath the plasma membrane after the replicated chromosomes have segregated. Constriction of the ring draws the plasma membrane inwards, closing the gap between the two daughter cells. One of our goals is to dissect the molecular mechanisms of ring assembly and constriction. To do this, we study early embryonic cell divisions in the nematode C. elegans, as actin, myosins and most of their regulators are well conserved in this system. Our favorite experimental approaches include live cell microscopy, genome engineering for generation of transgenic worms and structure-function studies, genetics and biochemistry. Using some of these approaches, we recently uncovered a robust gap repair mechanism in the contractile ring that ensures timely completion of cytokinesis (Silva et al., 2016). Gaining mechanistic insight into the process of cytokinesis is of significance for the understanding of tumorigenesis as failure of cytokinesis gives rise to polyploid cells, which have been postulated to be critical intermediates in the development of cancer. In addition, lessons learned about the contractile ring will help us understand other essential cellular processes that utilize acto-myosin contractile networks, namely tissue morphogenesis, wound healing, cell migration, and cell invasion. Work in our lab is funded by the European Research Council and FCT.
Equatorial Non-muscle Myosin II and Plastin Cooperate to Align and Compact F-actin Bundles in the Cytokinetic Ring. Frontiers in Cell and Developmental Biology8:, 2020. [Journal: Article] [CI: 1] [IF: 5,2 (*)]
DOI: 10.3389/fcell.2020.573393 SCOPUS: 85092498962. .
Osório D.S., Chan F.Y., Saramago J., Leite J., Silva A.M., Sobral A.F., Gassmann R., Carvalho A.X.,
Crosslinking activity of non-muscle myosin II is not sufficient for embryonic cytokinesis in C. elegans. Development146(21):, 2019. [Journal: Article] [CI: 4]
DOI: 10.1242/dev.179150 SCOPUS: 85074964249. .
Leite J., Osorio D.S., Sobral A.F., Silva A.M., Carvalho A.X.,
Network contractility during cytokinesisfrom molecular to global views. Biomolecules9(5):, 2019. [Journal: Article] [CI: 7] [IF: 4,1]
DOI: 10.3390/biom9050194 SCOPUS: 85066454203. .
Chan F.Y., Silva A.M., Saramago J., Pereira-Sousa J., Brighton H.E., Pereira M., Oegema K., Gassmann R., Carvalho A.X.,
The ARP2/3 complex prevents excessive formin activity during cytokinesis. Molecular Biology of the Cell30(1):96-107, 2019. [Journal: Article] [CI: 10] [IF: 3,8]
DOI: 10.1091/mbc.E18-07-0471 SCOPUS: 85059257752. .
Mangal S., Sacher J., Kim T., Osório D.S., Motegi F., Carvalho A.X., Oegema K., Zanin E.,
TPXL-1 activates Aurora A to clear contractile ring components from the polar cortex during cytokinesis. Journal of Cell Biology217(3):837-848, 2018. [Journal: Article] [CI: 27] [IF: 8,9]
DOI: 10.1083/jcb.201706021 SCOPUS: 85042867550. .
Thieleke-Matos C., Osório D.S., Carvalho A.X., Morais-de-Sá E.,
Emerging Mechanisms and Roles for Asymmetric Cytokinesis. International Review of Cell and Molecular Biology332:297-345, 2017. [Book Series: Chapter] [CI: 4] [IF: 3,6]
DOI: 10.1016/bs.ircmb.2017.01.004 SCOPUS: 85014702979. .
Silva A.M., Osório D.S., Pereira A.J., Maiato H., Pinto I.M., Rubinstein B., Gassmann R., Telley I.A., Carvalho A.X.,
Robust gap repair in the contractile ring ensures timely completion of cytokinesis. Journal of Cell Biology215(6):789-799, 2016. [Journal: Article] [CI: 12] [IF: 8]
DOI: 10.1083/jcb.201605080 SCOPUS: 85009223214. .
De Carvalho A.X., Maiato H., Maia A.F., Ribeiro S.A., Pontes P., Bickmore W., Earnshaw W.C., Sambade C.,
Reed-sternberg cells form by abscission failure in the presence of functional aurora B kinase. PLoS ONE10(5):, 2015. [Journal: Article] [CI: 10] [IF: 3,1]
DOI: 10.1371/journal.pone.0124629 SCOPUS: 84929096316. .
Davies T., Jordan S.N., Chand V., Sees J.A., Laband K., Carvalho A.X., Shirasu-Hiza M., Kovar D.R., Dumont J., Canman J.C.,
High-Resolution Temporal Analysis Reveals a Functional Timeline for the Molecular Regulation of Cytokinesis. Developmental Cell30(2):209-223, 2014. [Journal: Article] [CI: 47] [IF: 9,7]
DOI: 10.1016/j.devcel.2014.05.009 SCOPUS: 84904886021. .
Carvalho A., Desai A., Oegema K.,
Structural Memory in the Contractile Ring Makes the Duration of Cytokinesis Independent of Cell Size. Cell137(5):926-937, 2009. [Journal: Article] [CI: 145] [IF: 31,2]
DOI: 10.1016/j.cell.2009.03.021 SCOPUS: 65849336045. .
Lewellyn L., Carvalho A., Desai A., Maddox A.S., Oegema K.,
The chromosomal passenger complex and centralspindlin independently contribute to contractile ring assembly. Journal of Cell Biology193(1):155-169, 2011. [Journal: Article] [CI: 47] [IF: 10,3]
DOI: 10.1083/jcb.201008138 SCOPUS: 79955513613. .
Carvalho A., Olson S.K., Gutierrez E., Zhang K., Noble L.B., Zanin E., Desai A., Groisman A., Oegema K.,
Acute drug treatment in the early C. elegans embryo. PLoS ONE6(9):, 2011. [Journal: Article] [CI: 64] [IF: 4,1]
DOI: 10.1371/journal.pone.0024656 SCOPUS: 80052849441. .
Chan F.Y., Silva A.M., Carvalho A.X.,
Using the four-cell C. elegans embryo to study contractile ring dynamics during cytokinesis. Methods in Molecular Biology2101:297-325, 2020. [Book Series: Chapter]
DOI: 10.1007/978-1-0716-0219-5_18 SCOPUS: 85077269538. .