title: Both sequence and context are important for flagellar targeting of a glucose transporter.
abstract: Many of the cilia- and flagella-specific integral membrane proteins identified to date function to sense the extracellular milieu, and there is considerable interest in defining pathways for targeting such proteins to these sensory organelles. The flagellar glucose transporter of Leishmania mexicana, LmxGT1, is targeted selectively to the flagellar membrane, whereas two other isoforms, LmxGT2 and LmxGT3, are targeted to the pellicular plasma membrane of the cell body. To define the flagellar targeting signal, deletions and point mutations were generated in the N-terminal hydrophilic domain of LmxGT1, which mediates flagellar localization. Three amino acids, N95-P96-M97, serve critical roles in flagellar targeting, resulting in strong mistargeting phenotypes when mutagenized. However, to facilitate flagellar targeting of other non-flagellar membrane proteins, it was necessary to attach a larger region surrounding the NPM motif containing amino acids 81-113. Molecular modeling suggests that this region might present the critical NPM residues at the surface of the N-terminal domain. It is likely that the NPM motif is recognized by currently unknown protein-binding partners that mediate flagellar targeting of membrane-associated proteins.
authors.affiliation: Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR 97239, USA.
authors.forename: Khoa D
authors.initials: KD
authors.lastname: Tran
authors.forename: Dayana
authors.initials: D
authors.lastname: Rodriguez-Contreras
authors.forename: Ujwal
authors.initials: U
authors.lastname: Shinde
authors.forename: Scott M
authors.initials: SM
authors.lastname: Landfear
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D005407:Flagella / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007894:Leishmania mexicana / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary
chemical_list: D008565:Membrane Proteins; D009004:Monosaccharide Transport Proteins; C115490:glucose transporter, Leishmania; D049452:Green Fluorescent Proteins