title: Palmitoylation of stathmin family proteins domain A controls Golgi versus mitochondrial subcellular targeting.
abstract: BACKGROUND
  Precise localization of proteins to specialized subcellular domains is fundamental for proper neuronal development and function. The neural microtubule-regulatory phosphoproteins of the stathmin family are such proteins whose specific functions are controlled by subcellular localization. Whereas stathmin is cytosolic, SCG10, SCLIP and RB3/RB3'/RB3'' are localized to the Golgi and vesicle-like structures along neurites and at growth cones. We examined the molecular determinants involved in the regulation of this specific subcellular localization in hippocampal neurons in culture.
  
  
  RESULTS
  We show that their conserved N-terminal domain A carrying two palmitoylation sites is dominant over the others for Golgi and vesicle-like localization. Using palmitoylation-deficient GFP (green fluorescent protein) fusion mutants, we demonstrate that domains A of stathmin proteins have the particular ability to control protein targeting to either Golgi or mitochondria, depending on their palmitoylation. This regulation involves the co-operation of two subdomains within domain A, and seems also to be under the control of its SLD (stathmin-like domain) extension.
  
  
  CONCLUSIONS
  Our results unravel that, in specific biological conditions, palmitoylation of stathmin proteins might be able to control their targeting to express their functional activities at appropriate subcellular sites. They, more generally, open new perspectives regarding the role of palmitoylation as a signalling mechanism orienting proteins to their functional subcellular compartments.
authors.affiliation: Inserm, U839, 75005 Paris, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Chauvin
authors.forename: Fabienne E
authors.initials: FE
authors.lastname: Poulain
authors.forename: Sylvie
authors.initials: S
authors.lastname: Ozon
authors.forename: André
authors.initials: A
authors.lastname: Sobel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D054878:Lipoylation; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008868:Microtubule Proteins; D008928:Mitochondria / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D051381:Rats; D050777:Stathmin / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D029721:Drosophila Proteins; D008565:Membrane Proteins; D008868:Microtubule Proteins; D009414:Nerve Growth Factors; D050777:Stathmin; C512848:Stmn2 protein, rat; C491793:Stmn3 protein, mouse; C112286:Stmn4 protein, rat