Work

Kinesin-2 autoinhibition requires elbow phosphorylation

Year: 2024

Type: preprint

Abstract: Kinesin motor proteins facilitate microtubule-based transport by converting chemical energy into mechanic forces, but this activity is autoinhibited until cargo is loaded. Regulatory mechanisms underlying this autoinhibitory conformation are not well understood. Here, we show that a NEver in mitosis Kinase NEKL-3 directly phosphorylates a flexible elbow region between two coiled coil domains connecting the motor head and tail of an intraflagellar transport kinesin, OSM-3. The phosphor dead (PD) mutation, but not phosphor mimic (PM) mutation, induce constitutive motility of OSM-3 in vitro. Using knock-in animals, we discovered that both PD and PM mutations shorten the C. elegans sensory cilia. The constitutively active OSM-3PD fails to enter cilia and abnormally accumulates in neurites, mimicking another hyperactive mutation, OSM-3G444E. Conversely, OSM-3PM enters cilia but moves at a reduced speed, indicating an inhibitory role of elbow phosphorylation in kinesin motility. These findings highlight the crucial role of elbow phosphorylation in regulating kinesin autoinhibition.

Source: eLife

DOI: 10.7554/elife.103648

Authors: Guanghan Chen, Zhengyang Guo, Zhiwen Zhu, Shanshan Xie, Tianhua Zhou, Guangshuo Ou

Institutions: Tsinghua University, Soochow University, Children's Hospital of Zhejiang University, Zhejiang University

Language: English

Topic: Genetic and Kidney Cyst Diseases

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $2,500

Funder: National Natural Science Foundation of China