Cep57 Protein Is Required for Cytokinesis by Facilitating Central Spindle Microtubule Organization

Runsheng He,Qixi Wu,Haining Zhou,Ning Huang,Jianguo Chen,Junlin Teng

doi:10.1074/jbc.m112.441501

Abstract

Cytokinesis is the final stage of cell division in which the cytoplasm of a cell is divided into two daughter cells after the segregation of genetic material, and the central spindle and midbody are considered to be the essential structures required for the initiation and completion of cytokinesis. Here, we determined that the centrosome protein Cep57, which is localized to the central spindle and midbody, acts as a spindle organizer and is required for cytokinesis. Depletion of Cep57 disrupted microtubule assembly of the central spindle and further led to abnormal midbody localization of MKLP1, Plk1, and Aurora B, which resulted in cytokinesis failure and the formation of binuclear cells. Furthermore, we found that Cep57 directly recruited Tektin 1 to the midbody matrix to regulate microtubule organization. Thus, our data reveal that Cep57 is essential for cytokinesis via regulation of central spindle assembly and formation of the midbody.

Highlights

Cep57 has been shown to be a centrosome protein with microtubule-binding and microtubule-bundling activities
We further found that Cep57 was concentrated at the central spindle during anaphase and in the Flemming body of the midbody during cytokinesis (Fig. 1, A–C, arrows and arrowheads)
As Cep57 directly binds to microtubules and facilitates central spindle microtubule organization [15, 16], we investigated whether the central spindle and midbody localization of Cep57 is dependent on microtubules

Summary

Background

Cep has been shown to be a centrosome protein with microtubule-binding and microtubule-bundling activities. Results: Cep localizes to the midbody and plays roles in central spindle microtubule organization to ensure the completion of cytokinesis. We determined that the centrosome protein Cep, which is localized to the central spindle and midbody, acts as a spindle organizer and is required for cytokinesis. Depletion of Cep disrupted microtubule assembly of the central spindle and further led to abnormal midbody localization of MKLP1, Plk, and Aurora B, which resulted in cytokinesis failure and the formation of binuclear cells. A microtubule-associated protein, localizes to the spindle midzone through association with the MKLP1 (mitotic kinesin-like protein 1)-male germ cell Rac GTPase-activating protein centralspindlin complex, which is essential for the midbody structure and successful cytokinesis [3, 11]. We found that Cep localizes to the central spindle and midbody and acts as a factor of central spindle microtubule organization during cytokinesis

EXPERIMENTAL PROCEDURES

RESULTS

DISCUSSION