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The inhibition of polo kinase by matrimony maintains G2 arrest in the meiotic cell cycle.

Xiang Y, Takeo S, Florens L, Hughes SE, Huo LJ, Gilliland WD, Swanson SK, Teeter K, Schwartz JW, Washburn MP, Jaspersen SL, Hawley RS - PLoS Biol. (2007)

Bottom Line: Loss-of-function mtrm mutants result in precocious NEB.The meiotic defects observed in mtrm/+ heterozygotes are fully suppressed by reducing the dose of polo+, demonstrating that Mtrm acts as an inhibitor of Polo.Our data suggest a model in which the eventual activation of Cdc25 by an excess of Polo at stage 13 triggers NEB and entry into prometaphase.

View Article: PubMed Central - PubMed

Affiliation: Stowers Institute for Medical Research, Kansas City, Missouri, United States of America.

ABSTRACT
Many meiotic systems in female animals include a lengthy arrest in G2 that separates the end of pachytene from nuclear envelope breakdown (NEB). However, the mechanisms by which a meiotic cell can arrest for long periods of time (decades in human females) have remained a mystery. The Drosophila Matrimony (Mtrm) protein is expressed from the end of pachytene until the completion of meiosis I. Loss-of-function mtrm mutants result in precocious NEB. Coimmunoprecipitation experiments reveal that Mtrm physically interacts with Polo kinase (Polo) in vivo, and multidimensional protein identification technology mass spectrometry analysis reveals that Mtrm binds to Polo with an approximate stoichiometry of 1:1. Mutation of a Polo-Box Domain (PBD) binding site in Mtrm ablates the function of Mtrm and the physical interaction of Mtrm with Polo. The meiotic defects observed in mtrm/+ heterozygotes are fully suppressed by reducing the dose of polo+, demonstrating that Mtrm acts as an inhibitor of Polo. Mtrm acts as a negative regulator of Polo during the later stages of G2 arrest. Indeed, both the repression of Polo expression until stage 11 and the inactivation of newly synthesized Polo by Mtrm until stage 13 play critical roles in maintaining and properly terminating G2 arrest. Our data suggest a model in which the eventual activation of Cdc25 by an excess of Polo at stage 13 triggers NEB and entry into prometaphase.

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Related in: MedlinePlus

Oocyte Development in D. melanogasterThis figure displays a schematic depiction of oocyte development showing the timing (in hours) of the relevant stages. The end of meiotic prophase, as defined by SC dissolution, occurs at stages 5–6. By the end of stages 5–6, the chromosomes have condensed into a dense mass known as the karyosome, as pointed out by Mahowald and Kambysellis [2]. The karyosome remains compacted until stages 8–10, at which time it decondenses and a high level of transcription is observed. The chromosomes recompact during stages 11 and 12 to form a tight mass that is released into the cytoplasm upon NEB at stage 13. The end of pachytene is separated from NEB by approximately 40 h.
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pbio-0050323-g001: Oocyte Development in D. melanogasterThis figure displays a schematic depiction of oocyte development showing the timing (in hours) of the relevant stages. The end of meiotic prophase, as defined by SC dissolution, occurs at stages 5–6. By the end of stages 5–6, the chromosomes have condensed into a dense mass known as the karyosome, as pointed out by Mahowald and Kambysellis [2]. The karyosome remains compacted until stages 8–10, at which time it decondenses and a high level of transcription is observed. The chromosomes recompact during stages 11 and 12 to form a tight mass that is released into the cytoplasm upon NEB at stage 13. The end of pachytene is separated from NEB by approximately 40 h.

Mentions: The mechanism of the lengthy arrest in G2 that separates the end of pachytene from nuclear envelope breakdown (NEB)—which is a characterization of many female meiotic systems—has remained a mystery. One can imagine that both the maintenance and the termination of this arrest might involve either or both of two mechanisms— the transcriptional or translational repression of a protein that induces NEB, and thus meiotic entry, or the presence of an inhibitory protein that precludes entry into the first meiotic division. Because Drosophila females exhibit a prolonged G2 arrest (see Figure 1) and are amenable to both genetic and cytological analyses, they provide an ideal system in which to study this problem.


The inhibition of polo kinase by matrimony maintains G2 arrest in the meiotic cell cycle.

Xiang Y, Takeo S, Florens L, Hughes SE, Huo LJ, Gilliland WD, Swanson SK, Teeter K, Schwartz JW, Washburn MP, Jaspersen SL, Hawley RS - PLoS Biol. (2007)

Oocyte Development in D. melanogasterThis figure displays a schematic depiction of oocyte development showing the timing (in hours) of the relevant stages. The end of meiotic prophase, as defined by SC dissolution, occurs at stages 5–6. By the end of stages 5–6, the chromosomes have condensed into a dense mass known as the karyosome, as pointed out by Mahowald and Kambysellis [2]. The karyosome remains compacted until stages 8–10, at which time it decondenses and a high level of transcription is observed. The chromosomes recompact during stages 11 and 12 to form a tight mass that is released into the cytoplasm upon NEB at stage 13. The end of pachytene is separated from NEB by approximately 40 h.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2100146&req=5

pbio-0050323-g001: Oocyte Development in D. melanogasterThis figure displays a schematic depiction of oocyte development showing the timing (in hours) of the relevant stages. The end of meiotic prophase, as defined by SC dissolution, occurs at stages 5–6. By the end of stages 5–6, the chromosomes have condensed into a dense mass known as the karyosome, as pointed out by Mahowald and Kambysellis [2]. The karyosome remains compacted until stages 8–10, at which time it decondenses and a high level of transcription is observed. The chromosomes recompact during stages 11 and 12 to form a tight mass that is released into the cytoplasm upon NEB at stage 13. The end of pachytene is separated from NEB by approximately 40 h.
Mentions: The mechanism of the lengthy arrest in G2 that separates the end of pachytene from nuclear envelope breakdown (NEB)—which is a characterization of many female meiotic systems—has remained a mystery. One can imagine that both the maintenance and the termination of this arrest might involve either or both of two mechanisms— the transcriptional or translational repression of a protein that induces NEB, and thus meiotic entry, or the presence of an inhibitory protein that precludes entry into the first meiotic division. Because Drosophila females exhibit a prolonged G2 arrest (see Figure 1) and are amenable to both genetic and cytological analyses, they provide an ideal system in which to study this problem.

Bottom Line: Loss-of-function mtrm mutants result in precocious NEB.The meiotic defects observed in mtrm/+ heterozygotes are fully suppressed by reducing the dose of polo+, demonstrating that Mtrm acts as an inhibitor of Polo.Our data suggest a model in which the eventual activation of Cdc25 by an excess of Polo at stage 13 triggers NEB and entry into prometaphase.

View Article: PubMed Central - PubMed

Affiliation: Stowers Institute for Medical Research, Kansas City, Missouri, United States of America.

ABSTRACT
Many meiotic systems in female animals include a lengthy arrest in G2 that separates the end of pachytene from nuclear envelope breakdown (NEB). However, the mechanisms by which a meiotic cell can arrest for long periods of time (decades in human females) have remained a mystery. The Drosophila Matrimony (Mtrm) protein is expressed from the end of pachytene until the completion of meiosis I. Loss-of-function mtrm mutants result in precocious NEB. Coimmunoprecipitation experiments reveal that Mtrm physically interacts with Polo kinase (Polo) in vivo, and multidimensional protein identification technology mass spectrometry analysis reveals that Mtrm binds to Polo with an approximate stoichiometry of 1:1. Mutation of a Polo-Box Domain (PBD) binding site in Mtrm ablates the function of Mtrm and the physical interaction of Mtrm with Polo. The meiotic defects observed in mtrm/+ heterozygotes are fully suppressed by reducing the dose of polo+, demonstrating that Mtrm acts as an inhibitor of Polo. Mtrm acts as a negative regulator of Polo during the later stages of G2 arrest. Indeed, both the repression of Polo expression until stage 11 and the inactivation of newly synthesized Polo by Mtrm until stage 13 play critical roles in maintaining and properly terminating G2 arrest. Our data suggest a model in which the eventual activation of Cdc25 by an excess of Polo at stage 13 triggers NEB and entry into prometaphase.

Show MeSH
Related in: MedlinePlus