The detection of sweet-tasting compounds is mediated in large part by a heterodimeric receptor comprised of T1R2؉T1R3. Lactisole, a broad-acting sweet antagonist, suppresses the sweet taste of sugars, protein sweeteners, and artificial sweeteners. Lactisole's inhibitory effect is specific to humans and other primates; lactisole does not affect responses to sweet compounds in rodents. By heterologously expressing interspecies combinations of T1R2؉T1R3, we have determined that the target for lactisole's action is human T1R3. From studies with mouse/ human chimeras of T1R3, we determined that the molecular basis for sensitivity to lactisole depends on only a few residues within the transmembrane region of human T1R3. Alanine substitution of residues in the transmembrane region of human T1R3 revealed 4 key residues required for sensitivity to lactisole. In our model of T1R3's seven transmembrane helices, lactisole is predicted to dock to a binding pocket within the transmembrane region that includes these 4 key residues.Taste is a primal sense that enables diverse organisms to identify and ingest sweet-tasting nutritious foods and to reject bitter-tasting environmental poisons (1). Taste perception can be categorized into five distinct qualities: salty, sour, bitter, umami (amino acid taste), and sweet (1). Salty and sour depend on the actions of ion channels. Bitter, umami, and sweet depend on G-protein-coupled receptors (GPCRs) 1 and coupled signaling pathways. Sweet taste in large part depends on a heterodimeric receptor comprised of T1R2ϩT1R3 (2-5).The T1R taste receptors (T1R1, T1R2, and T1R3) are most closely related to metabotropic glutamate receptors (mGluRs), Ca 2ϩ -sensing receptors (CaSRs), and some pheromone receptors (6 -10). All of these receptors are class-C GPCRs, with the large clam shell-shaped extracellular amino-terminal domain (ATD) characteristic of this family. Following the ATD is a cysteine-rich region that connects the ATD to the heptahelical transmembrane domain (TMD); following the TMD is a short intracellular carboxyl-terminal tail. The solved crystal structure of the ATD of mGluR1 identifies a "Venus flytrap module" (VFTM) involved in ligand binding (11). The canonical agonist glutamate binds within the VFTM in a cleft formed by the two lobes of this module to stabilize a closed active conformation of the mGluR1 ATD. In contrast, several positive and negative allosteric modulators of class-C GPCRs have been identified and shown to act via binding not within the VFTM but instead within the TMD (12-16).Over the past few decades, multiple models of the sweet receptor's hypothetical ligand binding site have been generated based on the structures of existing sweeteners but without direct knowledge of the nature of the sweet receptor itself. A consensus feature of these models is the presence of A-H-B groups, in which the AH group is a hydrogen donor and the B group is an electronegative center. These models have explanatory and predictive value for some, but not all sweeteners, suggesting th...

The size and shape of the plant leaf is an important agronomic trait. To understand the molecular mechanism governing plant leaf shape, we characterized a classic rice (Oryza sativa) dwarf mutant named narrow leaf1 (nal1), which exhibits a characteristic phenotype of narrow leaves. In accordance with reduced leaf blade width, leaves of nal1 contain a decreased number of longitudinal veins. Anatomical investigations revealed that the culms of nal1 also show a defective vascular system, in which the number and distribution pattern of vascular bundles are altered. Map-based cloning and genetic complementation analyses demonstrated that Nal1 encodes a plant-specific protein with unknown biochemical function. We provide evidence showing that Nal1 is richly expressed in vascular tissues and that mutation of this gene leads to significantly reduced polar auxin transport capacity. These results indicate that Nal1 affects polar auxin transport as well as the vascular patterns of rice plants and plays an important role in the control of lateral leaf growth.