Unc5B interacts with FLRT3 and Rnd1 to modulate cell adhesion in Xenopus embryos

Area of Science:

• Developmental Biology
• Cell Biology
• Molecular Biology

Background:

• The FLRT protein family regulates FGF signaling, neurite outgrowth, cell sorting, and cell adhesion.
• Netrin receptors, such as Unc5B and Unc5D, are known for their roles in axon guidance and cell migration.

Purpose of the Study:

• To investigate the interaction between FLRT3 and Netrin receptors.
• To elucidate the functional consequences of FLRT3-Unc5B interaction in early development.
• To identify downstream mediators of FLRT3-induced cell deadhesion.

Main Methods:

• Expression screening to identify FLRT3 interactors.
• Overexpression and morpholino knockdown studies in Xenopus embryos.
• Analysis of cell adhesion, cell sorting, and developmental phenotypes.
• Biochemical assays to study protein-protein interactions and signaling pathways.

Main Results:

• Unc5B and Unc5D were identified as high-affinity FLRT3 interactors.
• Overexpression of Unc5B mimicked FLRT3 effects, and they synergized to induce cell deadhesion in Xenopus.
• Knockdown of Unc5B and FLRT3 caused synergistic developmental defects and morphogenetic abnormalities.
• The small GTPase Rnd1 physically and functionally interacts with Unc5B, mediating the cell adhesion effects.

Conclusions:

• FLRT3 and Unc5B form a complex that regulates cell adhesion during early Xenopus development.
• The FLRT3-Unc5B-Rnd1 pathway is essential for normal embryonic development and morphogenesis.
• This study reveals a novel mechanism for controlling cell adhesion through the interplay of FLRT3, Netrin receptors, and Rnd1.