Homodimeric Kinesin-2 KIF3CC Promotes Microtubule Dynamics

Abstract

KIF3C is one subunit of the functional microtubule-based kinesin-2 KIF3AC motor, an anterograde cargo transporter in neurons. However, KIF3C has also been implicated as an injury-specific kinesin that is a key regulator of axonal growth and regeneration by promoting microtubule dynamics for reorganization at the neuronal growth cone. To test its potential role as a modulator of microtubule dynamics in vitro, an engineered homodimeric KIF3CC was incorporated into a dynamic microtubule assay and examined by total internal reflection fluorescence microscopy. The results reveal that KIF3CC is targeted to the microtubule plus-end, acts as a potent catastrophe factor through an increase in microtubule catastrophe frequency, and does so by elimination of the dependence of the catastrophe rate on microtubule lifetime. Moreover, KIF3CC accelerates the catastrophe rate without altering the microtubule growth rate. Therefore, the ATP-promoted KIF3CC mechanism of catastrophe is different from the well-described catastrophe factors kinesin-13 MCAK and kinesin-8 Kip3/KIF18A. The properties of KIF3CC were not shared by heterodimeric KIF3AC and required the unique KIF3C-specific sequence extension in loop L11 at the microtubule interface. At the microtubule plus-end, the presence of KIF3CC resulted in modulation of the tapered structure typically seen in growing dynamic microtubules to microtubule blunt plus-ends. Overall our results implicate homodimeric KIF3CC as a unique promoter of microtubule catastrophe and substantiate its physiological role in cytoskeletal remodeling.