Figure 8.

Effects of GEF1-like activity modulation on the regulated secretory pathway. (A) During secretory granule maturation, a fraction of the soluble cargo is secreted through the constitutive-like route while the rest proceeds to full maturation and storage in mature granules. Constitutive-like release is thought to occur through vesicles that bud from ISGs (carrying with them partially processed cargo) and fuse with the plasma membrane either directly or through endosomal intermediates (not drawn) as suggested by experimental evidence from insulinoma cells (Turner and Arvan, 2000). The direct route from the TGN to the plasma membrane (constitutive secretion) is also depicted. (B) Activation of GEF1-like enzymes and their Rho substrates leads to increased constitutive-like release from immature granules, resulting in a reduction of secretory cargo content. (C) The opposite result is produced when endogenous GEF1-like activity is reduced; both constitutive-like and constitutive release may be inhibited (see effects on secreted GFP, Figure 6C), resulting in an increase in secretory cargo content.