Cell Division Mechanisms
ABOUT
Microtubule-based transport is essential for intracellular organization and cell division. Our group studies the function and regulation of cytoplasmic dynein 1, the principal microtubule minus end-directed motor in animal cells. We investigate the molecular mechanisms that enable dynein to transport a wide range of cargos, including organelles and mitotic chromosomes, and how its activity is coordinated with that of oppositely directed kinesins. Breakdown of bidirectional transport is a defining feature of many neurological disorders, underscoring the importance of understanding how these motor systems are controlled.
RESEARCH
Our research aims to define the molecular basis of dynein's functional versatility. We have focused on adaptor proteins that link the motor to its obligate activator dynactin and recruit the dynein–dynactin transport machinery to specific cargos. To dissect the functions and mechanisms of adaptor proteins in different cellular and developmental contexts, we use a multidisciplinary approach that combines live-cell fluorescence microscopy and genome editing in the roundworm Caenorhabditis elegans and cultured human cells with biochemical reconstitution of molecular interactions.
In dividing cells, we investigate how dynein adaptors contribute to spindle assembly and positioning to ensure accurate chromosome segregation. In interphase cells, we study adaptor scaffolds that coordinate bidirectional transport by coupling dynein to kinesins. Recent work has examined the neuronal lysosomal adaptor JIP3, which pairs dynein with kinesin-1. Efforts to discover novel dynein adaptors have led to the identification of the CDR2–kinectin adaptor module at the endoplasmic reticulum that we hypothesize coordinates opposing motors to regulate organelle architecture. Beyond uncovering fundamental mechanisms of intracellular transport, these studies may help illuminate disease mechanisms associated with defective motor regulation.
Team
Selected Publications
CDR2 is a dynein adaptor recruited by kinectin to regulate ER sheet organization. Journal of Cell Biology224(9):, 2025. [Journal: Article] [CI: 1] [IF: 6.4 (*)]
DOI: 10.1083/jcb.202411034 SCOPUS: 105010975079
Carvalho C., Moreira M., Barbosa D.J., Chan F.Y., Koehnen C.B., Teixeira V., Rocha H., Green M., Carvalho A.X., Cheerambathur D.K., Gassmann R.
ZYG-12/Hook’s dual role as a dynein adaptor for early endosomes and nuclei is regulated by alternative splicing of its cargo binding domain. Molecular Biology of the Cell36(2):, 2025. [Journal: Article] [CI: 3] [IF: 2.7 (*)]
DOI: 10.1091/mbc.E24-08-0364 SCOPUS: 85217518989
Singh K., Lau C.K., Manigrasso G., Gama J.B., Gassmann R., Carter A.P.
Molecular mechanism of dynein-dynactin complex assembly by LIS1. Science383(6690):1431-1448, 2024. [Journal: Article] [CI: 25] [IF: 45.8]
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: 5.1]
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: 5] [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: 16] [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: 32] [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: 5] [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: 52] [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: 38] [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: 52] [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: 32] [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: 97] [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: 23] [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: 33] [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
