Fission yeast TRP channel Pkd2p localizes to the cleavage furrow and regulates cell separation during cytokinesis

Abstract

Force plays a central role in separating daughter cells during cytokinesis, the last stage of cell division. However, the mechanism of force sensing during cytokinesis remains unknown. Here we discovered that Pkd2p, a putative force-sensing transient receptor potential channel, localizes to the cleavage furrow during cytokinesis of the fission yeast, Schizosaccharomyces pombe. Pkd2p, whose human homologues are associated with autosomal polycystic kidney disease, is an essential protein whose localization depends on the contractile ring and the secretory pathway. We identified and characterized a novel pkd2 mutant pkd2-81KD. The pkd2 mutant cells show signs of osmotic stress, including temporary shrinking, paused turnover of the cytoskeletal structures, and hyperactivated mitogen-activated protein kinase signaling. During cytokinesis, although the contractile ring constricts more rapidly in the pkd2 mutant than the wild-type cells (50% higher), the cell separation in the mutant is slower and often incomplete. These cytokinesis defects are also consistent with misregulated turgor pressure. Finally, the pkd2 mutant exhibits strong genetic interactions with two mutants of the septation initiation network pathway, a signaling cascade essential for cytokinesis. We propose that Pkd2p modulates osmotic homeostasis and is potentially a novel regulator of cytokinesis.

Fission yeast polycystin Pkd2p promotes the cell expansion and antagonizes the Hippo pathway SIN

“…Our recent study has identified another component of the cytokinesis signaling network Pkd2p, the fission yeast homologue of polycystin channels (Morris et al, 2019). Polycystins are conserved in most eukaryotes, even though they were discovered through the genetic studies of one of the most common human genetic disorders, ADPKD (Hughes et al, 1995; Mochizuki et al, 1996).…”

“…It concentrates at the cell tips during interphase and the cleavage furrow during cytokinesis (Morris et al, 2019). Knock-down of this essential gene leads to mis-regulation of the contractile ring constriction and failed cell separation (Morris et al, 2019). However, the molecular mechanism underlying the function of Pkd2p in cytokinesis remains unclear.…”

Microtubule nucleation promoters Mto1 and Mto2 regulate cytokinesis in fission yeast

“…Turgor pressure resists ingression, so mutations that reduce pressure or high osmolarity of the medium favor ingression ( Proctor et al. , 2012 ; Morris et al. , 2019 ).…”

Regulación de la citoquinesis por Rgf1 y la ruta de integridad

“…Sus respectivas deleciones originan leves defectos en septación y de pérdida de polaridad (Ren et al 2015). Recientemente se ha descrito que Pkd2, un receptor de potencial transitorio putativo, aparecería en la zona de división en la transición maduración/constricción y cuyo mutante tiene una constricción más rápida, presumiblemente por una reducida presión de turgencia (Morris et al 2019).…”

“…• Adaptar las condiciones internas. Las células podrían modificar, por ejemplo, su presión de turgencia para adaptarse al estrés antes de iniciar la constricción, algo que se ha visto influye en la velocidad de este proceso (Proctor et al 2012), que sería necesario para la separación celular (Atilgan et al 2015) y que podría relacionarse con fenotipos de multiseptación (Morris et al 2019). Este podría ser el caso para los compuestos probados que reducen la velocidad de constricción, pero parece poco probable en el caso del BP, pues la constricción progresa a la misma velocidad.…”