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.
Team
Selected Publications
Molecular mechanism of dynein-dynactin complex assembly by LIS1. Science383(6690):1431-1448, 2024. [Journal: Article] [CI: 8] [IF: 44.7 (*)]
DOI: 10.1126/science.adk8544 SCOPUS: 85189149237
Carvalho C., Barbosa D.J., Celestino R., Zanin E., Carvalho A.X., Gassmann R.
Dynein directs prophase centrosome migration to control the stem cell division axis in the developing Caenorhabditis elegans epidermis. Genetics226(3):, 2024. [Journal: Article] [IF: 3.3 (*)]
DOI: 10.1093/genetics/iyae005 SCOPUS: 85187136845
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: 4] [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: 12] [IF: 3.3]
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: 22] [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: 4] [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: 44] [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: 30] [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: 45] [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: 19] [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: 27] [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: 89] [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: 21] [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