title: The Lyn kinase C-lobe mediates Golgi export of Lyn through conformation-dependent ACSL3 association.
abstract: The Src-family tyrosine kinase Lyn has a role in signal transduction at the cytoplasmic face of the plasma membrane upon extracellular ligand stimulation. After synthesis in the cytoplasm, Lyn accumulates on the Golgi and is subsequently transported to the plasma membrane. However, the mechanism of Lyn trafficking remains elusive. We show here that the C-lobe of the Lyn kinase domain is associated with long-chain acyl-CoA synthetase 3 (ACSL3) on the Golgi in a manner that is dependent on Lyn conformation but is independent of its kinase activity. Formation of a closed conformation by CSK prevents Lyn from associating with ACSL3, resulting in blockade of Lyn export from the Golgi. Overexpression and knockdown of ACSL3 accelerates and blocks Golgi export of Lyn, respectively. The post-Golgi route of Lyn, triggered by ACSL3, is distinct from that of vesicular stomatitis virus glycoprotein (VSV-G) and of caveolin. Moreover, an ACSL3 mutant lacking the LR2 domain, which is required for the catalytic activity, retains the ability to associate with Lyn and accelerate Golgi export of Lyn. These results suggest that initiation of Golgi export of Lyn involves association of ACSL3 with the Lyn C-lobe, which is exposed to the molecular surface in an open conformation.
authors.affiliation: Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan.
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Obata
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Fukumoto
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nakayama
authors.forename: Takahisa
authors.initials: T
authors.lastname: Kuga
authors.forename: Naoshi
authors.initials: N
authors.lastname: Dohmae
authors.forename: Naoto
authors.initials: N
authors.lastname: Yamaguchi
mesh_terms: D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D002522:Chlorocebus aethiops; D003066:Coenzyme A Ligases / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006056:Golgi Apparatus; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D021381:Protein Transport / Q000187:drug effects / Q000235:genetics; D034741:RNA, Small Interfering; D013634:Tannins / Q000494:pharmacology; D019061:src-Family Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
chemical_list: D034741:RNA, Small Interfering; D013634:Tannins; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D003066:Coenzyme A Ligases; D000098859:Long-Chain-Fatty-Acid-CoA Ligase