title: Cholera toxin: an intracellular journey into the cytosol by way of the endoplasmic reticulum.
abstract: Cholera toxin (CT), an AB(5)-subunit toxin, enters host cells by binding the ganglioside GM1 at the plasma membrane (PM) and travels retrograde through the trans-Golgi Network into the endoplasmic reticulum (ER). In the ER, a portion of CT, the enzymatic A1-chain, is unfolded by protein disulfide isomerase and retro-translocated to the cytosol by hijacking components of the ER associated degradation pathway for misfolded proteins. After crossing the ER membrane, the A1-chain refolds in the cytosol and escapes rapid degradation by the proteasome to induce disease by ADP-ribosylating the large G-protein Gs and activating adenylyl cyclase. Here, we review the mechanisms of toxin trafficking by GM1 and retro-translocation of the A1-chain to the cytosol.
authors: GI Cell Biology, Children's Hospital (and Harvard Medical School), Boston, MA, USA. Naomi.Wernick@childrens.harvard.edu
authors: Naomi L B
authors: NL
authors: Wernick
authors: Daniel J-F
authors: DJ
authors: Chinnapen
authors: Jin Ah
authors: JA
authors: Cho
authors: Wayne I
authors: WI
authors: Lencer
mesh_terms: D002462:Cell Membrane / Q000378:metabolism; D002772:Cholera Toxin / Q000737:chemistry / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005677:G(M1) Ganglioside / Q000378:metabolism; D006801:Humans; D011487:Protein Conformation; D021381:Protein Transport
chemical_list: D005677:G(M1) Ganglioside; D002772:Cholera Toxin