Where Ideas grow

Cell Division Mechanisms

ABOUT

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.

 

 

RESEARCH

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

Celestino R., Henen M., Gama J., Carvalho C., McCabe M., Barbosa D., Born A., Nichols P., Carvalho A., 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: 1] [IF: 8,4 (*)]
DOI: 10.1371/journal.pbio.3000100 SCOPUS: 85060185140. .

Chan F., Silva A., Saramago J., Pereira-Sousa J., Brighton H., Pereira M., Oegema K., Gassmann R., Carvalho A.,
The ARP2/3 complex prevents excessive formin activity during cytokinesis. Molecular Biology of the Cell30(1):96-107, 2019. [Journal: Article] [IF: 3,9 (*)]
DOI: 10.1091/mbc.E18-07-0471 SCOPUS: 85059257752. .

Pereira C., Reis R., Gama J., Celestino R., Cheerambathur D., Carvalho A., 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: 3] [IF: 9,2]
DOI: 10.1016/j.cub.2018.08.056 SCOPUS: 85055739143. .

Rocha H., Maia A., 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., Celestino R., Carvalho A., 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: 6] [IF: 4,5]
DOI: 10.1242/jcs.212159 SCOPUS: 85042557731. .

Barbosa D., Duro J., Prevo B., Cheerambathur D., Carvalho A., 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: 10] [IF: 5,5]
DOI: 10.1371/journal.pgen.1006941 SCOPUS: 85026624927. .

Gama J., Pereira C., Simões P., Celestino R., Reis R., Barbosa D., Pires H., Carvalho C., Amorim J., Carvalho A., Cheerambathur D., 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: 30] [IF: 8,8]
DOI: 10.1083/jcb.201610108 SCOPUS: 85021847678. .

Silva A., Osório D., Pereira A., Maiato H., Pinto I., Rubinstein B., Gassmann R., Telley I., Carvalho A.,
Robust gap repair in the contractile ring ensures timely completion of cytokinesis. Journal of Cell Biology215(6):789-799, 2016. [Journal: Article] [CI: 6] [IF: 8]
DOI: 10.1083/jcb.201605080 SCOPUS: 85009223214. .

Holland A., Reis R., Niessen S., Pereira C., Andres D., Spielmann H., Cleveland D., 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: 15] [IF: 4]
DOI: 10.1091/mbc.E14-11-1560 SCOPUS: 84929440905. .

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