title: Alcohol induces Golgi fragmentation in differentiated PC12 cells by deregulating Rab1-dependent ER-to-Golgi transport.
abstract: In the present study, we analyze the effects of ethanol on the Golgi structure and membrane transport in differentiated PC12 cells, which are used as a model of neurons. Chronic exposure to moderate doses of ethanol induces Golgi fragmentation, a common characteristic of many neurodegenerative diseases. Alcohol impaired the lateral linking of stacks without causing microtubule damage. Extensive immunocytochemical and western blot analyses of representative Golgi proteins showed that few, but important, proteins are significantly affected. Thus, alcohol exposure induced a significant ER-to-Golgi transport delay, the retention of the GTPase Rab1 in the Golgi membranes and the accumulation of tethering factor p115 in the cytosol. These modifications would explain the observed fragmentation. The amount of p115 and the stacking protein GRASP65 increased in alcohol-treated cells, which might be a mechanism to reverse Golgi damage. Importantly, the overexpression of GTP-tagged Rab1 but not of a dominant-negative Rab1 mutant, restored the Golgi morphology, suggesting that this protein is the main target of alcohol. Taken together, our results support the view that alcohol and neurodegenerative diseases such as Parkinson have similar effects on intracellular trafficking and provide new clues on the neuropathology of alcoholism.
authors.affiliation: Department of Cell Biology and Histology, School of Medicine, University of Murcia, 30100 Murcia, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: Tomás
authors.forename: María Pilar
authors.initials: MP
authors.lastname: Marín
authors.forename: Emma
authors.initials: E
authors.lastname: Martínez-Alonso
authors.forename: Guillermo
authors.initials: G
authors.lastname: Esteban-Pretel
authors.forename: Alberto
authors.initials: A
authors.lastname: Díaz-Ruiz
authors.forename: Rafael
authors.initials: R
authors.lastname: Vázquez-Martínez
authors.forename: María M
authors.initials: MM
authors.lastname: Malagón
authors.forename: Jaime
authors.initials: J
authors.lastname: Renau-Piqueras
authors.forename: José A
authors.initials: JA
authors.lastname: Martínez-Menárguez
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D006056:Golgi Apparatus / Q000378:metabolism*; D000077614:Golgi Matrix Proteins; D008565:Membrane Proteins / Q000378:metabolism; D016716:PC12 Cells; D021381:Protein Transport; D051381:Rats; D033921:Vesicular Transport Proteins / Q000378:metabolism; D020761:rab1 GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D000077614:Golgi Matrix Proteins; C491577:Gorasp1 protein, rat; D008565:Membrane Proteins; D033921:Vesicular Transport Proteins; C091580:vesicular transport factor p115; D000431:Ethanol; D020761:rab1 GTP-Binding Proteins