STRIPAK regulates Slik localization to control mitotic morphogenesis and epithelial integrity

Area of Science:

• Cell Biology
• Molecular Biology
• Developmental Biology

Background:

• Proteins of the ezrin, radixin, and moesin (ERM) family are key regulators of cell and tissue morphogenesis.
• Moesin, the sole ERM protein in Drosophila, plays a critical role in mitotic morphogenesis and epithelial integrity.
• The Pp1-87B phosphatase dephosphorylates moesin, opposing its activation by the Ste20-like kinase Slik.

Purpose of the Study:

• To identify novel regulators of moesin activity and understand how the Slik-Pp1-87B signaling pathway is regulated.
• To investigate the role of the striatin-interacting phosphatase and kinase complex (STRIPAK) in moesin regulation.

Main Methods:

• Genome-wide RNAi screen in Drosophila to identify new regulators of moesin activity.
• Biochemical assays to determine the interaction between Slik and STRIPAK.
• Analysis of cell morphology and epithelial integrity in response to STRIPAK inhibition.

Main Results:

• Slik was identified as a component of the STRIPAK complex.
• The phosphatase activity of STRIPAK reduces Slik phosphorylation, promoting its cortical localization and moesin activation.
• Inhibition of STRIPAK phosphatase activity led to defects in mitotic cell morphology and epithelial tissue integrity.

Conclusions:

• The Slik-STRIPAK complex is a novel regulator of moesin activity.
• This signaling pathway is implicated in controlling multiple morphogenetic processes, including cell division and tissue organization.
• Understanding STRIPAK's role provides insights into the regulation of cytoskeletal dynamics and epithelial development.