Homodimeric Kinesin-2 KIF3CC Promotes Microtubule Dynamics

Area of Science:

• Cell Biology
• Neuroscience
• Molecular Motors

Background:

• KIF3C is a subunit of the kinesin-2 motor KIF3AC, involved in anterograde transport in neurons.
• KIF3C is also recognized for its role in axonal growth and regeneration, particularly in reorganizing microtubule dynamics at the neuronal growth cone.

Purpose of the Study:

• To investigate the role of engineered homodimeric KIF3C (KIF3CC) in modulating microtubule dynamics in vitro.
• To elucidate the mechanism by which KIF3CC affects microtubule growth and catastrophe.

Main Methods:

• Utilized a dynamic microtubule assay.
• Employed total internal reflection fluorescence microscopy to observe KIF3CC behavior.
• Analyzed microtubule catastrophe frequency and growth rates.

Main Results:

• KIF3CC targets the microtubule plus-end and acts as a potent catastrophe factor, increasing catastrophe frequency independently of microtubule lifetime.
• KIF3CC accelerates microtubule catastrophe without affecting the growth rate.
• Homodimeric KIF3CC, unlike heterodimeric KIF3AC, modulates microtubule plus-end structure, leading to blunt ends.

Conclusions:

• Homodimeric KIF3CC uniquely promotes microtubule catastrophe through a mechanism distinct from kinesin-13 MCAK and kinesin-8 Kip3/KIF18A.
• The KIF3C-specific sequence extension in loop L11 is crucial for KIF3CC's observed properties.
• These findings support a physiological role for homodimeric KIF3CC in cytoskeletal remodeling and neuronal regeneration.