Chemically induced proximity reveals mechanotransduction of a meiotic checkpoint at the nuclear envelope

Abstract

Successful sexual reproduction relies on robust quality control during meiosis. Assembly of the synaptonemal complex between homologous chromosomes (synapsis) regulates meiotic recombination and is crucial for accurate chromosome segregation in most eukaryotes. Synapsis defects can trigger cell cycle delays and, in some cases, apoptosis. Here, by developing and deploying a new chemically induced proximity system, we iden-tify key players in this quality control pathway in Caenorhabditis elegans. We find that persistence of the Polo-like kinase PLK-2 at pairing centers, specialized chromosome regions that interact with the nuclear envelope to promote homolog pairing and synapsis, induces apoptosis of oocytes by phosphorylating and destabilizing the nuclear lamina. Unexpectedly, we find that a mechanosensitive Piezo1/PEZO-1 channel localizes to the nuclear envelope and is required to transduce this signal to promote apoptosis. Thus, mechanosensitive ion channels play essential roles in detecting nuclear events and triggering apoptosis during gamete production. One-sentence summaryDestabilization of the nuclear lamina triggers Piezo-dependent germline apoptosis.