ABSTRACT
Cytokinesis is the final step of cell division following chromosome segregation that generates two daughter cells. The conserved exocyst complex is required for scission of the intercellular cytokinetic bridge, although the molecular mechanisms it employs in this process are unclear. We identify and validate the early endocytic GTPase Rab5 as interacting with the exocyst complex in mammalian cells. Rab5 localizes in the cytokinetic bridge and on the midbody ring in a manner similar to the exocyst complex. Depletion of Rab5 led to delayed abscission. Caenorhabditis elegans orthologs of both exocyst complex subunits and Rab5 localize along the cleavage furrow and are required for cytokinesis in early embryos. Cytokinetic cells depleted of either Rab5 or the exocyst subunits Exoc3 and Exoc4 showed impaired deposition of the endosomal sorting complexes required for transport (ESCRT) III subunits CHMP2B and/or CHMP4B near the midbody ring. The study reveals an evolutionarily conserved role for the early endocytic marker Rab5 in cytokinetic abscission. In addition, it uncovers a key requirement of the exocyst and Rab5 for the delivery of components of the membrane-severing ESCRT III machinery to complete cytokinesis.
Footnotes
Competing interests
The authors declare no competing or financial interests.
Author contributions
Conceptualization: S.V.S.M.; Validation: H.K., K.P., A.K., K.V., S.V.S.M.; Formal analysis: H.K., K.P., A.K., K.V., R.P., S.V.S.M.; Investigation: H.K., K.P., A.K., K.V., R.P., S.V.S.M.; Resources: K.P., S.V.S.M.; Data curation: H.K., K.P., A.K., K.V., S.V.S.M.; Writing - original draft: H.K., K.P., K.V., S.V.S.M.; Writing - review & editing: H.K., K.P., S.V.S.M.; Visualization: H.K., K.P., S.V.S.M.; Supervision: S.V.S.M.; Project administration: S.V.S.M.; Funding acquisition: K.P., S.V.S.M.
Funding
H.K. received fellowship support from the Regional Centre for Biotechnology. This work was supported by the Wellcome Trust/DBT India Alliance Fellowship [grant number IA/E/13/1/501] awarded to K.P. K.V. received support through a Young Investigator Award of the Regional Centre for Biotechnology. A.K. was supported by a fellowship from the Council of Scientific and Industrial Research (CSIR), India. R.P. received support from fellowships through the Department of Biotechnology, Ministry of Science and Technology (DBT) and the Indian Council of Medical research (ICMR), Government of India. This work was supported by institutional funding to S.V.S.M. from the Regional Centre for Biotechnology. Deposited in PMC for immediate release.
Supplementary information
Supplementary information available online at http://jcs.biologists.org/lookup/doi/10.1242/jcs.226001.supplemental
- Received September 29, 2018.
- Accepted June 14, 2019.
- © 2019. Published by The Company of Biologists Ltd
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
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