Akt may associate with insulin-responsive vesicles via interaction with sortilin.

Area of Science:

• Cell biology
• Molecular biology
• Metabolic signaling

Background:

• Insulin-responsive vesicles (IRVs) transport Glut4 to the plasma membrane.
• The insulin signaling pathway involves Akt, TBC1D4, and Rab10 on IRVs.
• The mechanism of Akt recruitment to IRVs is not fully understood.

Purpose of the Study:

• To elucidate the mechanism of Akt association with IRVs.
• To investigate the role of sortilin in Akt recruitment and insulin signaling.

Main Methods:

• Pull-down assays
• Immunofluorescence microscopy
• Cross-linking experiments
• Overexpression studies in adipocytes

Main Results:

• Akt is recruited to IRVs through interaction with the cytoplasmic C terminus of sortilin.
• Overexpression of full-length sortilin enhances insulin-stimulated TBC1D4 phosphorylation and glucose uptake.
• Overexpression of the sortilin cytoplasmic tail inhibits these processes.

Conclusions:

• Sortilin acts as a scaffold, mediating Akt recruitment to IRVs.
• IRVs are both a scaffold and a target for insulin signaling.
• This mechanism is critical for regulating glucose uptake.