Mutual antagonism between Hippo signaling and cyclin E drives intracellular pattern formation

Abstract

Not much is known about how organelles organize into patterns. In ciliates, the cortical pattern is propagated during “tandem duplication,” a cell division that remodels the parental cell into two daughter cells. A key step is the formation of the division boundary along the cell’s equator. In Tetrahymena thermophila, the cdaA alleles prevent the formation of the division boundary. We find that the CDAA gene encodes a cyclin E that accumulates in the posterior cell half, concurrently with accumulation of CdaI, a Hippo/Mst kinase, in the anterior cell half. The division boundary forms between the margins of expression of CdaI and CdaA, which exclude each other from their own cortical domains. The activities of CdaA and CdaI must be balanced to initiate the division boundary and to position it along the cell’s equator. CdaA and CdaI cooperate to position organelles near the new cell ends. Our data point to an intracellular positioning mechanism involving antagonistic Hippo signaling and cyclin E.

Immune Checkpoint Inhibitors in Triple Negative Breast Cancer Treatment: Promising Future Prospects

“…Natural killer (NK) cells form the first line natural defense against abnormal cells and infection with a wide range of pathogens. However, tumor cells have found ways to escape NK cell-mediated immunosurveillance such as the shedding of stress-inducible ligands MHC class I polypeptide-related sequence A (MICA) and MICB, which are exclusively expressed in stressed or transformed cells (151,152). This results in downregulation of the activating Natural killer group 2 member D (NKG2D) receptor and reduced susceptibility to NK cytotoxicity due to reduced cell surface density of the ligands.…”

Anterior–posterior pattern formation in ciliates

“…Another simpler explanation is that once the new posterior cell end emerges, CdaI cannot distinguish between the old and new posterior cell region due to the presence of its binding sites at both locations. Generally, the studied polarity factors tend to be present throughout the cell as documented most clearly for CdaA using super‐resolution microscopy (Jiang et al, 2020) and therefore their enrichment to specific cortical locations is not caused by diffusion barriers but rather by selective retention or biased transport.…”

“…the FZ position either depends on the OP position, or both rely on a common patterning mechanism). However, certain mutant combinations and drug treatments that affect phosphorylation states shift the relative positions of the OP and FZ [(Jiang et al, 2020; Kaczanowska et al, 2012) and see below]. Furthermore, a removal of the OP by dissection [in Stentor (Tartar, 1966)] or UV microbeam irradiation [in Glaucoma (Frankel, 1961)] fails to block the subsequent development of the FZ (Frankel, 1961; Tartar, 1966).…”

“…At this temperature the single mutant cdaA ‐ 1 does not divide, while the double mutant does. In the dividing double‐mutant the position of the FZ is often abnormal in relation to the OP and as a result the FZ cuts through the OP suggesting that under these conditions the two activities are not perfectly balanced (Jiang et al, 2020). This is reminiscent of the phenotype observed in cells treated with roscovitine, a CDK inhibitor (Kaczanowska et al, 2012).…”

“…There are several notable exceptions to this. In the double mutant ( cdaI ‐ 1 ; cdaA ‐ 1 ) raised at the restrictive temperature, CVPs sometimes develop posterior to the FZ (while the OP is positioned anterior to the FZ; Jiang et al, 2020). A hypomorphic single mutant cdaA ‐ 2 occasionally assembles CVPs posterior to the FZ, as well (Frankel, 1979).…”