CDK2 regulates nuclear envelope protein dynamics and telomere attachment in mouse meiotic prophase

J Cell Sci. 2015 Jan 1;128(1):88-99. doi: 10.1242/jcs.154922. Epub 2014 Nov 6.

Abstract

In most organisms, telomeres attach to the nuclear envelope at the onset of meiosis to promote the crucial processes of pairing, recombination and synapsis during prophase I. This attachment of meiotic telomeres is mediated by the specific distribution of several nuclear envelope components that interact with the attachment plates of the synaptonemal complex. We have determined by immunofluorescence and electron microscopy that the ablation of the kinase CDK2 alters the nuclear envelope in mouse spermatocytes, and that the proteins SUN1, KASH5 (also known as CCDC155) and lamin C2 show an abnormal cap-like distribution facing the centrosome. Strikingly, some telomeres are not attached to the nuclear envelope but remain at the nuclear interior where they are associated with SUN1 and with nuclear-envelope-detached vesicles. We also demonstrate that mouse testis CDK2 phosphorylates SUN1 in vitro. We propose that during mammalian prophase I the kinase CDK2 is a key factor governing the structure of the nuclear envelope and the telomere-led chromosome movements essential for homolog pairing.

Keywords: CDK2; Meiosis; Nuclear envelope; SUN1; Telomere.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Proteins / genetics
  • Cyclin-Dependent Kinase 2 / genetics
  • Cyclin-Dependent Kinase 2 / metabolism*
  • Cytoskeletal Proteins
  • Laminin / genetics
  • Laminin / metabolism
  • Male
  • Meiotic Prophase I / physiology*
  • Mice
  • Mice, Knockout
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Nuclear Envelope / genetics
  • Nuclear Envelope / metabolism*
  • Nuclear Proteins / genetics
  • Phosphorylation / physiology
  • Spermatocytes / cytology
  • Spermatocytes / metabolism*
  • Telomere / genetics
  • Telomere / metabolism*

Substances

  • Cell Cycle Proteins
  • Cytoskeletal Proteins
  • KASH5 protein, mouse
  • Laminin
  • Microtubule-Associated Proteins
  • Nuclear Proteins
  • SUN1 protein, mouse
  • lamin C2
  • Cdk2 protein, mouse
  • Cyclin-Dependent Kinase 2