The Role of the Striatin Family Proteins in Hippo Signaling and Cellular Regulation

The Striatin family proteins, including Striatin, SG2NA, and Zinedin, belong to the calmodulin-binding WD-40 repeat protein group and are components of the Striatin Interacting Phosphatase and Kinase (STRIPAK) complex. These proteins are known for their roles as scaffold proteins, facilitating various cellular pathways and regulating cell-cell interactions and signaling mechanisms. It has also been shown that Striatin is expressed in cell junctions, highlighting its potential role in maintaining cell integrity and communication. The current study aimed to elucidate the biological significance of the Striatin proteins by employing shRNA technology. This approach allowed us to modulate their expression levels and observe the resulting effects on cellular processes. Our data show that the Striatin family members significantly influence the Hippo signaling pathway by protecting phosphorylated YAP (pYAP) from proteasomal degradation, thus regulating the expression of Hippo target genes. This regulation impacts key cellular processes such as cell migration. RNA sequencing analyses of keratinocytes and fibroblasts depleted of Striatin proteins facilitated the identification of novel gene sets affected by the modulation of Striatin expression and provided insights into the broader impact of Striatin proteins and their roles in various cellular pathways.