title: Palmitoylation of LAT contributes to its subcellular localization and stability.
abstract: Palmitoylation is a protein modification for trafficking to lipid raft. Without palmitoylation, linker for activation of T cells (LAT), an adaptor molecule mediating T cell receptor signaling, is unable to localize in lipid rafts and to mediate T cell activation. We here show a novel role for palmitoylation in LAT trafficking to the plasma membrane and in the stability of the LAT protein. The human LAT mutant lacking palmitoylation was unable to traffic to the plasma membrane despite the presence of transmembrane portion. The mouse LAT mutant lacking palmitoylation was unstable and susceptible to degradation via the proteasome pathway. The human LAT mutant became unstable when the extracellular portion was swapped for that from mouse, indicating that both palmitoylation and the extracellular portion regulate the stability of LAT. These results suggest that palmitoylation has an important role in trafficking to the plasma membrane and the stability of LAT.
authors.affiliation: Department of Immunobiology, Medical Technology and Science, Osaka University Graduate School of Medicine, Osaka, Japan. natsuko@ims.u-tokyo.ac,jp
authors.forename: Natsuko
authors.initials: N
authors.lastname: Tanimura
authors.forename: Shin-ichiroh
authors.initials: S
authors.lastname: Saitoh
authors.forename: Sunao
authors.initials: S
authors.lastname: Kawano
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kosugi
authors.forename: Kensuke
authors.initials: K
authors.lastname: Miyake
mesh_terms: D000215:Acylation; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D006801:Humans; D019169:Jurkat Cells; D021962:Membrane Microdomains / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D019308:Palmitic Acid / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000502:physiology; D016415:Sequence Alignment
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C110810:LAT protein, human; C491734:Lat protein, mouse; D008565:Membrane Proteins; D010750:Phosphoproteins; D019308:Palmitic Acid