title: Molecular mechanisms of aquaporin biogenesis by the endoplasmic reticulum Sec61 translocon.
abstract: The past decade has witnessed remarkable advances in our understanding of aquaporin (AQP) structure and function. Much, however, remains to be learned regarding how these unique and vitally important molecules are generated in living cells. A major obstacle in this respect is that AQP biogenesis takes place in a highly specialized and relatively inaccessible environment formed by the ribosome, the Sec61 translocon and the ER membrane. This review will contrast the folding pathways of two AQP family members, AQP1 and AQP4, and attempt to explain how six TM helices can be oriented across and integrated into the ER membrane in the context of current (and somewhat conflicting) translocon models. These studies indicate that AQP biogenesis is intimately linked to translocon function and that the ribosome and translocon form a highly dynamic molecular machine that both interprets and is controlled by specific information encoded within the nascent AQP polypeptide. AQP biogenesis thus has wide ranging implications for mechanisms of translocon function and general membrane protein folding pathways.
authors.affiliation: Department of Biochemistry and Molecular Biology, Oregon Health and Sciences University Portland, Oregon, 3181 SW Sam Jackson Park Rd L-224 Portland, Oregon 97239, USA.
authors.forename: David
authors.initials: D
authors.lastname: Pitonzo
authors.forename: William R
authors.initials: WR
authors.lastname: Skach
mesh_terms: D000818:Animals; D051398:Aquaporin 1 / Q000737:chemistry / Q000378:metabolism*; D051401:Aquaporin 4 / Q000737:chemistry / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D011487:Protein Conformation; D017510:Protein Folding; D021381:Protein Transport; D012270:Ribosomes / Q000378:metabolism; D000069816:SEC Translocation Channels
chemical_list: D051401:Aquaporin 4; D008565:Membrane Proteins; D000069816:SEC Translocation Channels; D051398:Aquaporin 1