Domains controlling cell polarity and proliferation in the Drosophila tumor suppressor Scribble

Area of Science:

• Cell Biology
• Developmental Biology
• Genetics

Background:

• Cell polarity and proliferation are linked in animal tissues, but the underlying mechanisms remain unclear.
• Loss of the scribble (scrib) gene in Drosophila imaginal discs disrupts epithelial organization and leads to uncontrolled cell proliferation.
• Scrib is a multidomain scaffolding protein crucial for epithelial integrity.

Purpose of the Study:

• To investigate the specific domain requirements of Scrib for its functions in cell polarity, proliferation control, and epithelial organization.
• To elucidate the relationship between Scrib's structure and its role in maintaining tissue homeostasis.

Main Methods:

• Utilized an allelic series of scribble (scrib) mutations in Drosophila imaginal discs.
• Employed rescuing transgenes to assess the function of different Scrib domains.
• Analyzed epithelial organization, cell polarity, and proliferation rates in mutant and rescued tissues.

Main Results:

• The leucine-rich repeats (LRR) of Scrib are necessary and sufficient for establishing a polarized epithelial monolayer and are essential for proliferation control.
• The PDZ domains, while involved in recruiting Scrib to the junctional complex, are dispensable for overall epithelial organization.
• Absence of PDZ domains resulted in mild polarity defects and moderate overproliferation, but PDZ domains alone could not rescue Scrib function.

Conclusions:

• Scrib, through its LRR domains, primarily regulates cell proliferation by controlling apicobasal polarity.
• The LRR domains are critical for Scrib's tumor suppressor functions by maintaining epithelial polarity and organization.
• A model is proposed where Scrib's LRR activity is the key driver of proliferation control via polarity regulation.