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Co-expressed Cyclin D variants cooperate to regulate proliferation of germline nuclei in a syncytium.

Identifieur interne : 000D52 ( Main/Exploration ); précédent : 000D51; suivant : 000D53

Co-expressed Cyclin D variants cooperate to regulate proliferation of germline nuclei in a syncytium.

Auteurs : Gunasekaran Subramaniam [Norvège] ; Coen Campsteijn ; Eric M. Thompson

Source :

RBID : pubmed:25928155

Descripteurs français

English descriptors

Abstract

The role of the G1-phase Cyclin D-CDK 4/6 regulatory module in linking germline stem cell (GSC) proliferation to nutrition is evolutionarily variable. In invertebrate Drosophila and C. elegans GSC models, G1 is nearly absent and Cyclin E is expressed throughout the cell cycle, whereas vertebrate spermatogonial stem cells have a distinct G1 and Cyclin D1 plays an important role in GSC renewal. In the invertebrate, chordate, Oikopleura, where germline nuclei proliferate asynchronously in a syncytium, we show a distinct G1-phase in which 2 Cyclin D variants are co-expressed. Cyclin Dd, present in both somatic endocycling cells and the germline, localized to germline nuclei during G1 before declining at G1/S. Cyclin Db, restricted to the germline, remained cytoplasmic, co-localizing in foci with the Cyclin-dependent Kinase Inhibitor, CKIa. These foci showed a preferential spatial distribution adjacent to syncytial germline nuclei at G1/S. During nutrient-restricted growth arrest, upregulated CKIa accumulated in arrested somatic endoreduplicative nuclei but did not do so in germline nuclei. In the latter context, Cyclin Dd levels gradually decreased. In contrast, the Cyclin Dbβ splice variant, lacking the Rb-interaction domain and phosphodegron, was specifically upregulated and the number of cytoplasmic foci containing this variant increased. This upregulation was dependent on stress response MAPK p38 signaling. We conclude that under favorable conditions, Cyclin Dbβ-CDK6 sequesters CKIa in the cytoplasm to cooperate with Cyclin Dd-CDK6 in promoting germline nuclear proliferation. Under nutrient-restriction, this sequestration function is enhanced to permit continued, though reduced, cycling of the germline during somatic growth arrest.

DOI: 10.1080/15384101.2015.1041690
PubMed: 25928155


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Le document en format XML

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<term>Amino Acid Sequence</term>
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<term>Cell Nucleus (genetics)</term>
<term>Cell Nucleus (metabolism)</term>
<term>Cell Proliferation (physiology)</term>
<term>Chordata, Nonvertebrate</term>
<term>Cyclin D (biosynthesis)</term>
<term>Cyclin D (genetics)</term>
<term>Gene Expression Regulation</term>
<term>Genetic Variation (physiology)</term>
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<term>Animaux</term>
<term>Cellules germinales (métabolisme)</term>
<term>Cellules géantes (métabolisme)</term>
<term>Chordés invertébrés</term>
<term>Cycline D (biosynthèse)</term>
<term>Cycline D (génétique)</term>
<term>Données de séquences moléculaires</term>
<term>Noyau de la cellule (génétique)</term>
<term>Noyau de la cellule (métabolisme)</term>
<term>Prolifération cellulaire (physiologie)</term>
<term>Régulation de l'expression des gènes</term>
<term>Séquence d'acides aminés</term>
<term>Variation génétique (physiologie)</term>
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<term>Cyclin D</term>
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<div type="abstract" xml:lang="en">The role of the G1-phase Cyclin D-CDK 4/6 regulatory module in linking germline stem cell (GSC) proliferation to nutrition is evolutionarily variable. In invertebrate Drosophila and C. elegans GSC models, G1 is nearly absent and Cyclin E is expressed throughout the cell cycle, whereas vertebrate spermatogonial stem cells have a distinct G1 and Cyclin D1 plays an important role in GSC renewal. In the invertebrate, chordate, Oikopleura, where germline nuclei proliferate asynchronously in a syncytium, we show a distinct G1-phase in which 2 Cyclin D variants are co-expressed. Cyclin Dd, present in both somatic endocycling cells and the germline, localized to germline nuclei during G1 before declining at G1/S. Cyclin Db, restricted to the germline, remained cytoplasmic, co-localizing in foci with the Cyclin-dependent Kinase Inhibitor, CKIa. These foci showed a preferential spatial distribution adjacent to syncytial germline nuclei at G1/S. During nutrient-restricted growth arrest, upregulated CKIa accumulated in arrested somatic endoreduplicative nuclei but did not do so in germline nuclei. In the latter context, Cyclin Dd levels gradually decreased. In contrast, the Cyclin Dbβ splice variant, lacking the Rb-interaction domain and phosphodegron, was specifically upregulated and the number of cytoplasmic foci containing this variant increased. This upregulation was dependent on stress response MAPK p38 signaling. We conclude that under favorable conditions, Cyclin Dbβ-CDK6 sequesters CKIa in the cytoplasm to cooperate with Cyclin Dd-CDK6 in promoting germline nuclear proliferation. Under nutrient-restriction, this sequestration function is enhanced to permit continued, though reduced, cycling of the germline during somatic growth arrest.</div>
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