Fission yeast polycystin Pkd2p promotes cell size expansion and antagonizes the Hippo-related SIN pathway.

Polycystins are conserved mechanosensitive channels whose mutations lead to the common human renal disorder autosomal dominant polycystic kidney disease (ADPKD). Previously, we discovered that the plasma membrane-localized fission yeast polycystin homolog Pkd2p is an essential protein required for cytokinesis; however, its role remains unclear. Here, we isolated a novel temperature-sensitive pkd2 mutant, pkd2-B42. Among the strong growth defects of this mutant, the most striking was that many mutant cells often lost a significant portion of their volume in just 5 min followed by a gradual recovery, a process that we termed 'deflation'. Unlike cell lysis, deflation did not result in plasma membrane rupture and occurred independently of cell cycle progression. The tip extension of pkd2-B42 cells was 80% slower than that of wild-type cells, and their turgor pressure was 50% lower. Both pkd2-B42 and the hypomorphic depletion mutant pkd2-81KD partially rescued mutants of the septation initiation network (SIN), a yeast Hippo-related signaling pathway, by preventing cell lysis, enhancing septum formation and doubling the number of Sid2p and Mob1p molecules at the spindle pole bodies. We conclude that Pkd2p promotes cell size expansion during interphase by regulating turgor pressure and antagonizes the SIN during cytokinesis. This article has an associated First Person interview with the first author of the paper.

The mechanosensitive Pkd2 channel modulates the recruitment of myosin II and actin to the cytokinetic contractile ring.

Cytokinesis, the last step in cell division, separate daughter cells through the force produced by an actomyosin contractile ring assembled at the equatorial plane. In fission yeast cells, the ring helps recruit a mechanosensitive ion channel Pkd2 to the cleavage furrow, whose activation by membrane tension promotes calcium influx and daughter cell separation. However, it is unclear how the activities of Pkd2 may affect the actomyosin ring. Here, through both microscopic and genetic analyses of a hypomorphic mutant of the essential pkd2 gene, we examine its potential role in assembling and constricting the contractile ring. The pkd2-81KD mutation significantly increased the number of type II myosin heavy chain Myo2 (+20%), its regulatory light chain Rlc1 (+37%) and actin (+20%) molecules in the ring, compared to the wild type. Consistent with a regulatory role of Pkd2 in the ring assembly, we identified a strong negative genetic interaction between pkd2-81KD and the temperature-sensitive mutant myo2-E1 . The pkd2-81KD myo2-E1 cells often failed to assemble a complete contractile ring. We conclude that Pkd2 modulates the recruitment of type II myosin and actin to the contractile ring, suggesting a novel calcium- dependent mechanism regulating the actin cytoskeletal structures during cytokinesis.