Are Wnts Retrogradely Transported to the ER?

Area of Science:

• Cell biology
• Molecular biology
• Developmental biology

Background:

• Wntless (Wls) is an evolutionarily conserved Wnt secretion factor.
• Wntless facilitates the secretion of Wingless (Wg) in Drosophila.
• Wingless (Wg) possesses a C-terminal dilysine motif (KKVY) potentially involved in retrograde transport.

Purpose of the Study:

• To investigate the role of Drosophila miR-307a in endoplasmic reticulum (ER) stress.
• To explore the relationship between Wnt secretion and ER stress.
• To examine the potential retrograde transport of Wingless (Wg) from the Golgi to the ER.

Main Methods:

• Analysis of miR-307a function in Drosophila wingless (wg)-expressing cells.
• Investigating the impact of Wntless (Wls) suppression on ER stress.
• Phenotypic analysis of Wnt secretion impairment in Drosophila and mammalian cells.

Main Results:

• Drosophila miR-307a suppresses Wntless (Wls), inducing ER stress in wingless (wg)-expressing cells.
• Impairment of Wnt secretion, including Wnt5a in mammalian cells, phenocopies ER stress.
• A putative C-terminal dilysine motif (KKVY) in Wg suggests potential Golgi-to-ER retrograde transport.

Conclusions:

• Wntless suppression by miR-307a is linked to ER stress.
• The study suggests a novel Golgi-to-ER retrograde transport route for Wg.
• ER stress may be a consequence of impaired Wnt secretion, potentially due to ER retention.