FIGURE 6.

Hypothetical model for CLASP2 in insulin action. The identification of the involvement of CLASP2 in insulin-stimulated glucose uptake has led to the following model. Upon insulin activation of the insulin receptor, IRS-1-mediated activation of PI-3K results in a localized increase in PIP₃ at the plasma membrane. PIP₃ then recruits LL5α (also known as PHLDB1), a known binding partner for CLASP2. This is followed by CLASP2 binding to LL5α, thereby directing the GLUT4 vesicle to the insulin-responsive landing zone on the cortical PM. This in turn leads to the docking and fusion of the GLUT4 vesicle with the PM, mediated by the SNARE protein complex, composed of VAMP2 within the IRV and both syntaxin 4 and SNAP23 on the PM.