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The Scribble module regulates retromer-dependent endocytic trafficking during epithelial polarization.

Geert de Vreede1, Joshua D Schoenfeld1, Sarah L Windler1

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Development (Cambridge, England)
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PubMed
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The Scribble module regulates cell polarity by influencing endosomal trafficking via the retromer pathway. This study reveals Scrib module proteins are crucial for proper retromer localization and cargo sorting in Drosophila.

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Background:

  • Scribble (Scrib) module proteins are critical regulators of cell polarity.
  • The precise mechanisms by which endocytosis influences cell polarity are not fully understood.
  • The connection between Scrib module proteins and membrane trafficking pathways remains largely unknown.

Purpose of the Study:

  • To investigate the role of the Scribble module in regulating membrane traffic and its connection to cell polarity.
  • To identify specific endocytic pathways influenced by Scrib module proteins.
  • To elucidate how Scrib module proteins affect the localization and function of endocytic machinery.

Main Methods:

  • Utilized Drosophila melanogaster as a model organism.
  • Generated and analyzed Scribble module mutants and AP-2 endocytosis mutants.
  • Examined endocytosis, endolysosomal transport, and retromer pathway function.
  • Investigated genetic interactions between Scrib module components and retromer pathway proteins.
  • Assessed the localization of retromer components and cargo.

Main Results:

  • Scribble module mutants exhibit intact cargo internalization and endolysosomal transport but show defective traffic of retromer pathway cargo.
  • Strong genetic interactions were observed between Scrib module components and retromer pathway elements.
  • The Scribble module is essential for the correct localization of retromer to endosomes.
  • Scrib module proteins promote cargo sorting into the retromer pathway through both aPKC-dependent and -independent mechanisms.

Conclusions:

  • The Scribble module regulates epithelial polarity by modulating endocytic itineraries, particularly those involving the retromer pathway.
  • Scrib module proteins influence the trafficking of Crumbs and other retromer-dependent cargo.
  • This study establishes a novel link between the Scribble module and the retromer endosomal trafficking system, providing insights into polarity regulation.