PLK1 regulates centrosome migration and spindle dynamics in male mouse meiosis

• Published in: EMBO reports 2021-04, Vol.22 (4), p.e51030-n/a
• Main Authors: Alfaro, Enrique, López-Jiménez, Pablo, González-Martínez, José, Malumbres, Marcos, Suja, José A, Gómez, Rocío
• Format: Article
• Language: English
• Subjects: Ablation; Animals; Assembly; AURKA; Cell Cycle Proteins - genetics; Cell division; Centrosome; Centrosomes; Cytokinesis; EMBO05; EMBO06; Gametocytes; Kinases; Localization; Male; Males; Maturation; Meiosis; meiotic spindle; Mice; PCM; PLK1; Polo-Like Kinase 1; Prophase; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins - genetics; Reproduction (copying); Somatic cells; Spermatocytes; Spermatogenesis; Spindle Apparatus; Spindles; Tubules; Vertebrates; Zebrafish; Zygotene
• ISSN: 1469-221X; 1469-3178
• DOI: 10.15252/embr.202051030

Cell division requires the regulation of karyokinesis and cytokinesis, which includes an essential role of the achromatic spindle. Although the functions of centrosomes are well characterised in somatic cells, their role during vertebrate spermatogenesis remains elusive. We have studied the dynamics of the meiotic centrosomes in male mouse during both meiotic divisions. Results show that meiotic centrosomes duplicate twice: first duplication occurs in the leptotene/zygotene transition, while the second occurs in interkinesis. The maturation of duplicated centrosomes during the early stages of prophase I and II are followed by their separation and migration to opposite poles to form bipolar spindles I and II. The study of the genetic mouse model Plk1 (Δ/Δ) indicates a central role of Polo-like kinase 1 in pericentriolar matrix assembly, in centrosome maturation and migration, and in the formation of the bipolar spindles during spermatogenesis. In addition, in vitro inhibition of Polo-like kinase 1 and Aurora A in organotypic cultures of seminiferous tubules points out to a prominent role of both kinases in the regulation of the formation of meiotic bipolar spindles. Synopsis Polo-like Kinase 1 (PLK1) has a key role in the regulation of centrosome dynamics in male mouse meiosis. PLK1 participates in pericentriolar matrix (PCM) assembly, centrosome maturation and migration, and in the formation of the meiotic bipolar spindle. Centrosomes duplicate twice during male mouse meiosis: in the leptotene/zygotene transition and during interkinesis. Meiotic centrosomes separate during diplotene and during interkinesis/prophase II to facilitate the assembly of bipolar meiotic spindles. Genetic ablation or chemical inhibition or PLK1 result in monopolar spindles in both meiotic divisions in mouse spermatocytes. In vitro inhibition of PLK1 and AURKA suggest an important role of both kinases in formation of meiotic bipolar spindles. Inhibition of PLK1 and AURKA impairs KIF11 localization to monopolar spindles. Graphical Abstract Polo-like Kinase 1 (PLK1) has a key role in the regulation of centrosome dynamics in male mouse meiosis. PLK1 participates in pericentriolar matrix (PCM) assembly, centrosome maturation and migration, and in the formation of the meiotic bipolar spindle.