Pentagone internalises glypicans to fine-tune multiple signalling pathways

Area of Science:

• Developmental Biology
• Molecular Signaling
• Cell Biology

Background:

• Precise regulation of signaling pathways, particularly bone morphogenetic protein (BMP)/Decapentaplegic (Dpp) signaling, is vital for embryonic development, tissue patterning, and growth.
• Glypicans, such as Dally and Dally-like protein (Dlp), are crucial co-receptors that modulate BMP/Dpp signaling gradients.
• Understanding the feedback mechanisms controlling morphogen signaling is essential for deciphering developmental processes.

Purpose of the Study:

• To investigate the function of the secreted protein Pentagone (Pent) in regulating BMP/Dpp morphogen signaling during Drosophila wing development.
• To elucidate the mechanism by which Pent controls the levels of BMP/Dpp co-receptors at the cell surface.
• To determine the role of Pent in other signaling pathways, such as Wingless (Wg) signaling.

Main Methods:

• Utilized Drosophila melanogaster as a model organism for studying developmental signaling.
• Investigated the interaction of Pentagone with Dpp co-receptors (Dally and Dlp) using techniques assessing protein internalization and degradation.
• Employed genetic approaches to examine the requirement for dynamin, Rab5, and clathrin in Pent-mediated glypican endocytosis.
• Assessed the impact of Pent on BMP signaling and Wg signaling pathways.

Main Results:

• Pentagone mediates the internalization and degradation of Dally and Dlp, key co-receptors for BMP/Dpp signaling.
• Pent-induced glypican endocytosis requires dynamin and Rab5, but is independent of clathrin and active BMP signaling.
• Pent regulates the BMP reception system by modulating the levels of co-receptors at the plasma membrane, influencing Dpp gradient establishment.
• Pent is also required for Wingless (Wg) signaling, highlighting its broader role in developmental pathways.

Conclusions:

• Pentagone acts as a negative feedback regulator of BMP/Dpp signaling by promoting glypican co-receptor internalization and degradation.
• This mechanism provides a novel way to fine-tune morphogen signaling, crucial for establishing long-range signaling gradients and proper tissue development.
• Pent's involvement in both BMP and Wg signaling underscores its importance in coordinating multiple developmental pathways.