An interphase pool of KIF11 localizes at the basal bodies of primary cilia and a reduction in KIF11 expression alters cilia dynamics

Abigail A Zalenski,Shubhra Majumder,Monica Venere,Kuntal De

doi:10.1038/s41598-020-70787-4

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.

Highlights

KIF11 is a homotetrameric kinesin that peaks in protein expression during mitosis
KIF11 localizes to the basal body of primary cilia in GBM cells
Akin to what we identified in GBM cancer stem cells, we found that KIF11 was localized near the basal body of primary cilia in RPE1 cells (Fig. 2a,b)

Summary

Introduction

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. 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. We found that this interphase pool of KIF11 was responsible for driving tumor cell invasion and process formation[4] In addition to these reported non-mitotic roles of KIF11, there are two patient populations that have reported mutations in the KIF11 gene. The primary cilium is a sensory organelle that can project from many different cell types, and is required for developmental signaling pathways such as sonic hedgehog[17,18] Despite these overlapping symptoms, KIF11 has never been implicated as a regulator of primary cilia. The presence of KIF11 outside of mitosis, combined with the patient mutations and phenotypes, led us to hypothesize that KIF11 plays a role in regulating primary cilia dynamics

Methods

Results

Conclusion