title: Control of Tobacco mosaic virus movement protein fate by CELL-DIVISION-CYCLE protein48.
abstract: Like many other viruses, Tobacco mosaic virus replicates in association with the endoplasmic reticulum (ER) and exploits this membrane network for intercellular spread through plasmodesmata (PD), a process depending on virus-encoded movement protein (MP). The movement process involves interactions of MP with the ER and the cytoskeleton as well as its targeting to PD. Later in the infection cycle, the MP further accumulates and localizes to ER-associated inclusions, the viral factories, and along microtubules before it is finally degraded. Although these patterns of MP accumulation have been described in great detail, the underlying mechanisms that control MP fate and function during infection are not known. Here, we identify CELL-DIVISION-CYCLE protein48 (CDC48), a conserved chaperone controlling protein fate in yeast (Saccharomyces cerevisiae) and animal cells by extracting protein substrates from membranes or complexes, as a cellular factor regulating MP accumulation patterns in plant cells. We demonstrate that Arabidopsis (Arabidopsis thaliana) CDC48 is induced upon infection, interacts with MP in ER inclusions dependent on the MP N terminus, and promotes degradation of the protein. We further provide evidence that CDC48 extracts MP from ER inclusions to the cytosol, where it subsequently accumulates on and stabilizes microtubules. We show that virus movement is impaired upon overexpression of CDC48, suggesting that CDC48 further functions in controlling virus movement by removal of MP from the ER transport pathway and by promoting interference of MP with microtubule dynamics. CDC48 acts also in response to other proteins expressed in the ER, thus suggesting a general role of CDC48 in ER membrane maintenance upon ER stress.
authors.affiliation: Institut de Biologie Moléculaire des Plantes, Unité Propre de Recherche 2357 Centre National de la Recherche Scientifique, Université de Strasbourg, 67000 Strasbourg, France.
authors.forename: Annette
authors.initials: A
authors.lastname: Niehl
authors.forename: Khalid
authors.initials: K
authors.lastname: Amari
authors.forename: Dalya
authors.initials: D
authors.lastname: Gereige
authors.forename: Katrin
authors.initials: K
authors.lastname: Brandner
authors.forename: Yves
authors.initials: Y
authors.lastname: Mély
authors.forename: Manfred
authors.initials: M
authors.lastname: Heinlein
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D017360:Arabidopsis / Q000378:metabolism* / Q000821:virology*; D029681:Arabidopsis Proteins / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress; D049452:Green Fluorescent Proteins / Q000378:metabolism; D002479:Inclusion Bodies / Q000378:metabolism; D010935:Plant Diseases / Q000821:virology; D053830:Plant Viral Movement Proteins / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D059748:Proteolysis; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D014026:Nicotiana / Q000821:virology; D014027:Tobacco Mosaic Virus / Q000378:metabolism*
chemical_list: D029681:Arabidopsis Proteins; D015415:Biomarkers; D018797:Cell Cycle Proteins; D053830:Plant Viral Movement Proteins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D000074183:ATPases Associated with Diverse Cellular Activities; C525275:CDC48A protein, Arabidopsis