title: Subcellular Golgi localization of stathmin family proteins is promoted by a specific set of DHHC palmitoyl transferases.
abstract: Protein palmitoylation is a reversible lipid modification that plays critical roles in protein sorting and targeting to specific cellular compartments. The neuronal microtubule-regulatory phosphoproteins of the stathmin family (SCG10/stathmin 2, SCLIP/stathmin 3, and RB3/stathmin 4) are peripheral proteins that fulfill specific and complementary roles in the formation and maturation of the nervous system. All neuronal stathmins are localized at the Golgi complex and at vesicles along axons and dendrites. Their membrane anchoring results from palmitoylation of two close cysteine residues present within their homologous N-terminal targeting domains. By preventing palmitoylation with 2-bromopalmitate or disrupting the integrity of the Golgi with brefeldin A, we were able to show that palmitoylation of stathmins 2 and 3 likely occurs at the Golgi and is crucial for their specific subcellular localization and trafficking. In addition, this membrane binding is promoted by a specific set of palmitoyl transferases that localize with stathmins 2 and 3 at the Golgi, directly interact with them, and enhance their membrane association. The subcellular membrane-associated microtubule-regulatory activity of stathmins might then be fine-tuned by extracellular stimuli controlling their reversible palmitoylation, which can be viewed as a crucial regulatory process for specific and local functions of stathmins in neurons.
authors.affiliation: INSERM U 839, Université Pierre et Marie Curie, UMR-S839, and Institut du Fer à Moulin, F-75005, Paris, France.
authors.forename: Aurore D
authors.initials: AD
authors.lastname: Levy
authors.forename: Véronique
authors.initials: V
authors.lastname: Devignot
authors.forename: Yuko
authors.initials: Y
authors.lastname: Fukata
authors.forename: Masaki
authors.initials: M
authors.lastname: Fukata
authors.forename: André
authors.initials: A
authors.lastname: Sobel
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Chauvin
mesh_terms: D000217:Acyltransferases / Q000378:metabolism*; D000818:Animals; D020126:Brefeldin A / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D019084:Fluorescent Antibody Technique, Indirect; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006801:Humans; D054878:Lipoylation / Q000187:drug effects; D009474:Neurons / Q000378:metabolism; D010168:Palmitates / Q000494:pharmacology; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D021381:Protein Transport; D051381:Rats; D050777:Stathmin / Q000378:metabolism*
chemical_list: D010168:Palmitates; D050777:Stathmin; C022776:2-bromopalmitate; D020126:Brefeldin A; D000217:Acyltransferases