creating a
healthier future

Cell Division Mechanisms


Cytoplasmic dynein 1 (dynein), a mega-dalton complex of 6 distinct subunits, is the predominant microtubule minus end-directed motor in animals and participates in a wide range of essential cellular activities, ranging from the transport of proteins, mRNA, and vesicles to nuclear migration and cell division. Our group is interested in the regulatory mechanisms that give rise to dynein's functional diversity.




We use live-cell fluorescence microscopy, genetics, and biochemical approaches in the roundworm Caenorhabditis elegans and human cultured cells to study the roles and molecular mechanisms of co-factors that associate with dynein to modulate localization, interaction with cargo, and motor activity. We have been investigating how the 3-subunit Rod-Zw10-Zwilch complex and the adaptor protein Spindly regulate dynein function at the kinetochore, the site on chromosomes where spindle microtubules attach to drive the segregation of sister chromatids during cell division. Adaptors like Spindly have a dual role: they bring dynein together with its essential processivity factor dynactin, which is itself a multi-subunit complex, and they establish the link to diverse cargo. By studying how different adaptor families interact with dynein and dynactin, we hope to uncover general and cargo-specific mechanisms underlying the assembly and activation of the dynein-dynactin transport machinery in dividing and non-dividing cells. Mutations in dynein and its regulators are known to cause neurodegenerative disease, making a molecular understanding of dynein-driven transport medically relevant.

Immunofluorescence image of the first embryonic division of the roundworm Caenorhabditis elegans showing the microtubule cytoskeleton (green) and the segregating chromosomes (purple).


Selected Publications

Rocha H., Simões P.A., Budrewicz J., Lara-Gonzalez P., Carvalho A.X., Dumont J., Desai A., Gassmann R.,
Nuclear-enriched protein phosphatase 4 ensures outer kinetochore assembly prior to nuclear dissolution. Journal of Cell Biology222(3):, 2023. [Journal: Article] [CI: 1] [IF: 7,8 (*)]
DOI: 10.1083/jcb.202208154 SCOPUS: 85147234335

Gassmann R.,
Dynein at the kinetochore. Journal of Cell Science136(5):, 2023. [Journal: Review] [CI: 2] [IF: 4 (*)]
DOI: 10.1242/jcs.220269 SCOPUS: 85149427755

Celestino R., Gama J.B., Castro-Rodrigues A.F., Barbosa D.J., Rocha H., D’Amico E.A., Musacchio A., Carvalho A.X., Morais-Cabral J.H., Gassmann R.,
JIP3 interacts with dynein and kinesin-1 to regulate bidirectional organelle transport. Journal of Cell Biology221(8):, 2022. [Journal: Article] [CI: 11] [IF: 7,8]
DOI: 10.1083/jcb.202110057 SCOPUS: 85134435160

Barbosa D.J., Teixeira V., Duro J., Carvalho A.X., Gassmann R.,
Dynein-dynactin segregate meiotic chromosomes in C. elegans spermatocytes. Development148(3):, 2021. [Journal: Article] [CI: 3] [IF: 6,9]
DOI: 10.1242/dev.197780 SCOPUS: 85102094952

Kops G.J.P.L., Gassmann R.,
Crowning the Kinetochore: The Fibrous Corona in Chromosome Segregation. Trends in Cell Biology30(8):653-667, 2020. [Journal: Review] [CI: 33] [IF: 20,8]
DOI: 10.1016/j.tcb.2020.04.006 SCOPUS: 85084228116

Celestino R., Henen M.A., Gama J.B., Carvalho C., McCabe M., Barbosa D.J., Born A., Nichols P.J., Carvalho A.X., Gassmann R., Vögeli B.,
A transient helix in the disordered region of dynein light intermediate chain links the motor to structurally diverse adaptors for cargo transport. PLoS Biology17(1):, 2019. [Journal: Article] [CI: 24] [IF: 7,1]
DOI: 10.1371/journal.pbio.3000100 SCOPUS: 85060185140

Pereira C., Reis R.M., Gama J.B., Celestino R., Cheerambathur D.K., Carvalho A.X., Gassmann R.,
Self-Assembly of the RZZ Complex into Filaments Drives Kinetochore Expansion in the Absence of Microtubule Attachment. Current Biology28(21):3408-3421.e8, 2018. [Journal: Article] [CI: 41] [IF: 9,2]
DOI: 10.1016/j.cub.2018.08.056 SCOPUS: 85055739143

Rocha H., Maia A.F., Gassmann R.,
Data Descriptor: A genome-scale RNAi screen for genetic interactors of the dynein co-factor nud-2 in Caenorhabditis elegans. Scientific Data5:, 2018. [Journal: Article] [CI: 1] [IF: 5,9]
DOI: 10.1038/sdata.2018.47 SCOPUS: 85044305058

Simões P.A., Celestino R., Carvalho A.X., Gassmann R.,
NudE regulates dynein at kinetochores but is dispensable for other dynein functions in the C. elegans early embryo. Journal of Cell Science131(1):, 2018. [Journal: Article] [CI: 18] [IF: 4,5]
DOI: 10.1242/jcs.212159 SCOPUS: 85042557731

Barbosa D.J., Duro J., Prevo B., Cheerambathur D.K., Carvalho A.X., Gassmann R.,
Dynactin binding to tyrosinated microtubules promotes centrosome centration in C. elegans by enhancing dynein-mediated organelle transport. PLoS Genetics13(7):, 2017. [Journal: Article] [CI: 25] [IF: 5,5]
DOI: 10.1371/journal.pgen.1006941 SCOPUS: 85026624927

Gama J.B., Pereira C., Simões P.A., Celestino R., Reis R.M., Barbosa D.J., Pires H.R., Carvalho C., Amorim J., Carvalho A.X., Cheerambathur D.K., Gassmann R.,
Molecular mechanism of dynein recruitment to kinetochores by the Rod-Zw10-Zwilch complex and Spindly. Journal of Cell Biology216(4):943-960, 2017. [Journal: Article] [CI: 81] [IF: 8,8]
DOI: 10.1083/jcb.201610108 SCOPUS: 85021847678

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: 19] [IF: 8]
DOI: 10.1083/jcb.201605080 SCOPUS: 85009223214

Holland A.J., Reis R.M., Niessen S., Pereira C., Andres D.A., Spielmann H.P., Cleveland D.W., Desai A., Gassmann R.,
Preventing farnesylation of the dynein adaptor Spindly contributes to the mitotic defects caused by farnesyltransferase inhibitors. Molecular Biology of the Cell26(10):1845-1856, 2015. [Journal: Article] [CI: 30] [IF: 4]
DOI: 10.1091/mbc.E14-11-1560 SCOPUS: 84929440905

Maia A.F., Tanenbaum M.E., Galli M., Lelieveld D., Egan D.A., Gassmann R., Sunkel C.E., Van Den Heuvel S., Medema R.H.,
Genome-wide RNAi screen for synthetic lethal interactions with the C. elegans kinesin-5 homolog BMK-1. Scientific Data2:, 2015. [Journal: Article] [CI: 8]
DOI: 10.1038/sdata.2015.20 SCOPUS: 84960970688

Ongoing Projects

Regulation of axonal transport by motor-cargo adaptors
Reference: PTDC/BIA-CEL/1321/2021
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: FCT - Fundação para a Ciência e a Tecnologia
From 01-JAN-22 to 31-DEC-24