CDK2 regulates nuclear envelope protein dynamics and telomere attachment in mouse meiotic prophase.
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.
Unidad de Biología Celular, Departamento de Biología, Facultad de Ciencias, Universidad Autónoma de Madrid, E-28049 Madrid, Spain.
Alberto
A
Viera
Department of Cell and Developmental Biology, Biocenter, University of Würzburg, D-97074 Würzburg, Germany.
Manfred
M
Alsheimer
Unidad de Biología Celular, Departamento de Biología, Facultad de Ciencias, Universidad Autónoma de Madrid, E-28049 Madrid, Spain.
Rocío
R
Gómez
Unidad de Biología Celular, Departamento de Biología, Facultad de Ciencias, Universidad Autónoma de Madrid, E-28049 Madrid, Spain.
Inés
I
Berenguer
Biotechnology Program, Centro Nacional de Investigaciones Oncológicas, E-28029 Madrid, Spain.
Sagrario
S
Ortega
Molecular Oncology Program, Centro Nacional de Investigaciones Oncológicas, E-28029 Madrid, Spain.
Catherine E
CE
Symonds
Molecular Oncology Program, Centro Nacional de Investigaciones Oncológicas, E-28029 Madrid, Spain.
David
D
Santamaría
Department of Cell and Developmental Biology, Biocenter, University of Würzburg, D-97074 Würzburg, Germany.
Ricardo
R
Benavente
Unidad de Biología Celular, Departamento de Biología, Facultad de Ciencias, Universidad Autónoma de Madrid, E-28049 Madrid, Spain jose.suja@uam.es.
José A
JA
Suja
D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins; D007797:Laminin / Q000235:genetics / Q000378:metabolism; D008297:Male; D049469:Meiotic Prophase I / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009685:Nuclear Envelope / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics; D010766:Phosphorylation / Q000502:physiology; D013090:Spermatocytes / Q000166:cytology / Q000378:metabolism*; D016615:Telomere / Q000235:genetics / Q000378:metabolism*; D034882:Lamins
D018797:Cell Cycle Proteins; D051357:Cyclin-Dependent Kinase 2; D003598:Cytoskeletal Proteins; D007797:Laminin; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; C575644:KASH5 protein, mouse; C464932:SUN1 protein, mouse; C087355:lamin C2; D034882:Lamins; C495893:Cdk2 protein, mouse
CDK2; Meiosis; Nuclear envelope; SUN1; Telomere