Abstract
KIF11 is a homotetrameric kinesin that peaks in protein expression during mitosis. It is a known mitotic regulator, and it is well-described that KIF11 is necessary for the formation and maintenance of the bipolar spindle. However, there has been a growing appreciation for non-mitotic roles for KIF11. KIF11 has been shown to function in such processes as axon growth and microtubule polymerization. We previously demonstrated that there is an interphase pool of KIF11 present in glioblastoma cancer stem cells that drives tumor cell invasion. Here, we identified a previously unknown association between KIF11 and primary cilia. We confirmed that KIF11 localized to the basal bodies of primary cilia in multiple cell types, including neoplastic and non-neoplastic cells. Further, we determined that KIF11 has a role in regulating cilia dynamics. Upon the reduction of KIF11 expression, the number of ciliated cells in asynchronously growing populations was significantly increased. We rescued this effect by the addition of exogenous KIF11. Lastly, we found that depleting KIF11 resulted in an increase in cilium length and an attenuation in the kinetics of cilia disassembly. These findings establish a previously unknown link between KIF11 and the dynamics of primary cilia and further support non-mitotic functions for this kinesin.
| Original language | English |
|---|---|
| Article number | 13946 |
| Journal | Scientific Reports |
| Volume | 10 |
| Issue number | 1 |
| DOIs | |
| State | Published - Dec 1 2020 |
Funding
The authors thank Dr. Jeremy Rich (UC San Diego) for the kind gift of the GBM 08-387 cells. The authors also thank Dr. Liwen Zhang of the Proteomics Shared Resource at The Ohio State Comprehensive Cancer Center and Dr. Belinda Willard of the Lerner Research Institute Mass Spectrometry Laboratory for Protein Sequencing at the Cleveland Clinic Foundation for sample processing and analysis. We also thank members of the Venere lab and Dr. Matthew Summers for insightful discussion and constructive comments on the manuscript. This work was supported by a Research Scholar Grant RSG-18-066-01-TBG from the American Cancer Society, the National Institutes of Health Grant R03CA227206, and funds from The Ohio State University Comprehensive Cancer Center/Department of Radiation Oncology (MV); and an Ohio State University Graduate School Dean’s Distinguished University Fellowship (AZ). The Fusion Lumos instrument from the Lerner Research Institute Mass Spectrometry Laboratory for Protein Sequencing at the Cleveland Clinic Foundation was purchased via a National Institutes of Health shared instrument Grant, 1S10OD023436-01. Research reported in the publication was supported by The Ohio State University Comprehensive Cancer Center and the National Institutes of Health under Grant Number P30 CA016058. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
| Funders | Funder number |
|---|---|
| Ohio State University Comprehensive Cancer Center | P30 CA016058 |
| Ohio State University Comprehensive Cancer Center/Department | |
| Ohio State University Graduate School Dean’s Distinguished University | |
| National Institutes of Health | R03CA227206 |
| American Cancer Society | RSG-18-066-01-TBG |
