Figure 2. The Mammalian GLUT4 Asymmetric Vesicular Targeting Mechanism as a Model for the Localization of the Auxin Efflux Carrier.

A vesicular cycling mechanism similar to the mammalian insulin-inducible GLUT4 glucose transporter trafficking system is suggested by recent studies of PIN protein localization and protein interactions with auxin transport inhibitors. Sequence homologies and analogous functions of many of the protein components of the two systems further suggest parallel mechanisms. An external signal (hormone binding) triggers a phosphatidylinositol/phosphorylation cascade that activates asymmetric vesicular trafficking by (1) causing relocation of an inhibitory ARF-GEF protein (GRP1 or GNOM) from an endomembrane compartment to phosphatidylinositol triphosphate-enriched plasma membranes and (2) phosphorylating both a vesicular aminopeptidase (IRAP or AtAPM1) and the Vamp2 adaptor protein. Vesicles then traffic on actin filaments to a plasma membrane docking site, where Vamp2 interacts with Syntaxin 4/Knolle to initiate docking with Munc18c/Keule and subsequent vesicle fusion. Endocytotic vesicles enriched in dynamin and -adaptin traffic back to the endosomal compartment in a similar actin-dependent manner. AtAPM1, Arabidopsis thaliana microsomal aminopeptidase; GRP1 ARF-GEF, general receptor for phosphoinositides ADP ribosylation factor guanine nucleotide exchange factor; IRAP, insulin-responsive aminopeptidase; Munc18c, mammalian homolog of unc18c; PID, PINOID; PI3K, phosphatidylinositol 3-kinase; PKB, protein kinase B/KT; PKC, protein kinase C; PP2a, phosphatase 2a; RCN1, root curling in NPA-1 PP2a; Vamp2, vesicle-associated membrane protein 2 (v-SNARE2).