KIF5B modulates central spindle organization in late-stage cytokinesis in chondrocytes

Huiyan Gan,Wenqian Xue,Kathryn S E Cheah,Ya Gao,Jiandong Huang,Guixia Zhu,Danny Chan

doi:10.1186/s13578-019-0344-5

Abstract

BackgroundThe growth plate is a special region of the cartilage that drives longitudinal growth of long bones. Proliferating chondrocytes in the growth plate, arranged in columns, divide perpendicular to the long axis of the growth plate then intercalate to re-align with parental columns. Which molecular partners maintain growth plate columnar structures and chondrocyte cytokinesis has not been fully revealed. It is reported that kinesin family member 3A (KIF3A), a subunit of kinesin-2, plays an important role in maintaining columnar organization in growth plates via controlling primary cilia formation and cell proliferation.ResultHere we identify kinesin family member 5B (KIF5B), the heavy chain of kinesin-1, a ubiquitously expressed motor protein for anterograde intracellular transport along the microtubule network, as a key modulator of cytokinesis in chondrocytes via maintenance of central spindle organization. We show that KIF5B is concentrated in the central spindle during cytokinesis in both primary chondrocytes and chondrogenic ATDC5 cells.ConclusionThe failure of cytokinesis in KIF5B null chondrocytes leads to incomplete cell rotation, disrupting proliferation and differentiation, and results in a disorganized growth plate.

Highlights

The growth plate is regarded as a functional unit of endochondral ossification
The failure of cytokinesis in kinesin family member 5B (KIF5B) null chondrocytes leads to incomplete cell rotation, disrupting proliferation and differentiation, and results in a disorganized growth plate
KIF5B depletion in chondrocytes leads to growth plate abnormalities Kif5b mutant mice were viable and had a normal life span, but they were smaller in stature owing to shortened spine vertebrae and long bones (Fig. 1a, b)

Summary

Introduction

The growth plate is regarded as a functional unit of endochondral ossification. Growth plate dysfunction usually leads to bone abnormality, like bone growth retardation [19, 20, 32]. The continuous proliferation and differentiation of chondrocytes function as an engine for the Kinesin is one of the motor proteins that transport various cargoes along microtubules to specific destinations within the cell. It is reported that Kif3a mutant chondrocytes show loss of primary cilia, reduced proliferation, defective cell rotation and accelerated differentiation, resulting in disrupted columnar organization in the growth plate and post-natal dwarfism [36]. Proliferating chondrocytes in the growth plate, arranged in columns, divide perpendicular to the long axis of the growth plate intercalate to re-align with parental columns. It is reported that kinesin family member 3A (KIF3A), a subunit of kinesin-2, plays an important role in maintaining columnar organization in growth plates via controlling primary cilia formation and cell proliferation

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Discussion

Conclusion