A farnesyl-dependent structural role for CENP-E in expansion of the fibrous corona

Author:

Wu Jingchao123ORCID,Raas Maximilian W.D.134ORCID,Alcaraz Paula Sobrevals35ORCID,Vos Harmjan R.35ORCID,Tromer Eelco C.6ORCID,Snel Berend4ORCID,Kops Geert J.P.L.123ORCID

Affiliation:

1. Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences 1 , Utrecht, Netherlands

2. University Medical Center Utrecht 2 , Utrecht, Netherlands

3. Oncode Institute 3 , Utrecht, Netherlands

4. Utrecht University 4 Theoretical Biology and Bioinformatics, Department of Biology, Faculty of Science, , Utrecht, Netherlands

5. Center for Molecular Medicine, Molecular Cancer Research, University Medical Center Utrecht 5 , Utrecht, Netherlands

6. Cell Biochemistry, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen 6 Faculty of Science and Engineering, , Groningen, Netherlands

Abstract

Correct chromosome segregation during cell division depends on proper connections between spindle microtubules and kinetochores. During prometaphase, kinetochores are temporarily covered with a dense protein meshwork known as the fibrous corona. Formed by oligomerization of ROD/ZW10/ZWILCH-SPINDLY (RZZ-S) complexes, the fibrous corona promotes spindle assembly, chromosome orientation, and spindle checkpoint signaling. The molecular requirements for formation of the fibrous corona are not fully understood. Here, we show that the fibrous corona depends on the mitotic kinesin CENP-E and that poorly expanded fibrous coronas after CENP-E depletion are functionally compromised. This previously unrecognized role for CENP-E does not require its motor activity but instead is driven by farnesyl modification of its C-terminal kinetochore- and microtubule-binding domain. We show that in cells, CENP-E binds Spindly and recruits RZZ-S complexes to ectopic locations in a farnesyl-dependent manner. CENP-E is recruited to kinetochores following RZZ-S, and—while not required for RZZ-S oligomerization per se—promotes subsequent fibrous corona expansion. Our comparative genomics analyses suggest that the farnesylation motif in CENP-E orthologs emerged alongside the full RZZ-S module in an ancestral lineage close to the fungi–animal split (Obazoa), revealing potential conservation of the mechanisms for fibrous corona formation. Our results show that proper spindle assembly has a potentially conserved non-motor contribution from the kinesin CENP-E through stabilization of the fibrous corona meshwork during its formation.

Funder

European Research Council

KWF Kankerbestrijding

Netherlands Organisation for Scientific Research

Publisher

Rockefeller University Press

Subject

Cell Biology

Reference82 articles.

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