Exportin-mediated nucleocytoplasmic transport maintains Pch2 homeostasis during meiosis

The meiotic recombination checkpoint reinforces the order of events during meiotic prophase I, ensuring the accurate distribution of chromosomes to the gametes. The AAA+ ATPase Pch2 remodels the Hop1 axial protein enabling adequate levels of Hop1-T318 phosphorylation to support the ensuing checkpoint response. While these events are localized at chromosome axes, the checkpoint activating function of Pch2 relies on its cytoplasmic population. In contrast, forced nuclear accumulation of Pch2 leads to checkpoint inactivation. Here, we reveal the mechanism by which Pch2 travels from the cell nucleus to the cytoplasm to maintain Pch2 cellular homeostasis. Leptomycin B treatment provokes the nuclear accumulation of Pch2, indicating that its nucleocytoplasmic transport is mediated by the Crm1 exportin recognizing proteins containing Nuclear Export Signals (NESs). Consistently, leptomycin B leads to checkpoint inactivation and impaired Hop1 axial localization. Pch2 nucleocytoplasmic traffic is independent of its association with Zip1 and Orc1. We also identify a functional NES in the non-catalytic N-terminal domain of Pch2 that is required for its nucleocytoplasmic trafficking and proper checkpoint activity. In sum, we unveil another layer of control of Pch2 function during meiosis involving nuclear export via the exportin pathway that is crucial to maintain the critical balance of Pch2 distribution among different cellular compartments.

 

Comments:

That's a very detailed and scientific explanation of the mechanisms involving Pch2 during meiosis! It seems like your research delves into the intricate processes of cellular regulation during this critical stage. The interplay between the AAA+ ATPase Pch2, Hop1 protein, and the meiotic recombination checkpoint highlights the importance of maintaining proper cellular localization for functional activity.

The discovery of the role of Crm1 exportin in mediating Pch2's nucleocytoplasmic transport, particularly through its recognition of Nuclear Export Signals (NESs), is intriguing. It appears that this transport mechanism plays a crucial part in regulating Pch2's function and its impact on the meiotic recombination checkpoint.

Identifying the specific NES within the non-catalytic N-terminal domain of Pch2 that is necessary for its proper trafficking and checkpoint activity is a significant advancement in understanding the control mechanisms governing Pch2 distribution within different cellular compartments.

This research sheds light on yet another layer of complexity in cellular regulation during meiosis, emphasizing the critical balance required for the precise functioning of proteins like Pch2. It seems like your findings contribute significantly to our understanding of the intricate processes governing meiotic events and the checkpoints involved in ensuring accurate chromosome distribution.

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Cat.No.	Product Name	Information
S7580	Leptomycin B	Leptomycin B (LMB, CI 940, Elactocin, Mantuamycin, NSC 364372) is a potent antifungal antibiotic isolated from Streptomyces and acts as a specific inhibitor of the nuclear export factor CRM1. Leptomycin B rapidly induces cytotoxic effects in cancer cell lines via covalent inhibition of CRM1 with IC50 values of 0.1 nM–10 nM.

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CRM1