Nek2 kinase displaces distal appendages from the mother centriole prior to mitosis

Author:

Viol Linda12,Hata Shoji3ORCID,Pastor-Peidro Ana3,Neuner Annett3,Murke Florian4ORCID,Wuchter Patrick5,Ho Anthony D.5,Giebel Bernd4,Pereira Gislene123ORCID

Affiliation:

1. Centre for Organismal Studies, University of Heidelberg, Heidelberg, Germany

2. German Cancer Research Centre, German Cancer Research Centre-Centre for Cell and Molecular Biology Alliance, Heidelberg, Germany

3. Centre for Cell and Molecular Biology, German Cancer Research Centre-Centre for Cell and Molecular Biology Alliance, University of Heidelberg, Heidelberg, Germany

4. Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

5. Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany

Abstract

Distal appendages (DAs) of the mother centriole are essential for the initial steps of ciliogenesis in G1/G0 phase of the cell cycle. DAs are released from centrosomes in mitosis by an undefined mechanism. Here, we show that specific DAs lose their centrosomal localization at the G2/M transition in a manner that relies upon Nek2 kinase activity to ensure low DA levels at mitotic centrosomes. Overexpression of active Nek2A, but not kinase-dead Nek2A, prematurely displaced DAs from the interphase centrosomes of immortalized retina pigment epithelial (RPE1) cells. This dramatic impact was also observed in mammary epithelial cells with constitutively high levels of Nek2. Conversely, Nek2 knockout led to incomplete dissociation of DAs and cilia in mitosis. As a consequence, we observed the presence of a cilia remnant that promoted the asymmetric inheritance of ciliary signaling components and supported cilium reassembly after cell division. Together, our data establish Nek2 as an important kinase that regulates DAs before mitosis.

Funder

Deutsche Forschungsgemeinschaft

Publisher

Rockefeller University Press

Subject

Cell Biology

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