title: The water channel aquaporin-1 partitions into exosomes during reticulocyte maturation: implication for the regulation of cell volume.
abstract: Aquaporin-1 (AQP-1), the universal water channel, is responsible for rapid response of cell volume to changes in plasma tonicity. In the membrane of the red cell the concentration of the protein is tightly controlled. Here, we show that AQP-1 is partially lost during in vitro maturation of mouse reticulocytes and that it is associated with exosomes, released throughout this process. AQP-1 in young reticulocytes localizes to the plasma membrane and also in endosomal compartments and exosomes, formed both in vitro and in vivo. During maturation a part of the total pool of AQP-1 is differentially sorted and released via the exosomal pathway. A proteasome inhibitor, MG132, suppresses secretion of AQP-1, implying that ubiquitination is a sorting signal for its release. We further show that modulation of medium tonicity in vitro regulates the secretion of AQP-1, thus showing that extracellular osmotic conditions can drive sorting of selected proteins by the exosomal pathway. These results lead us to suggest that AQP-1 sorting into exosomes may be the mechanism by which the reticulocyte adapts to environmental changes during its maturation.
authors.affiliation: Red Cell Physiology Laboratory, New York Blood Center, New York, NY 10065, USA. lblanc@nybloodcenter.org
authors.forename: Lionel
authors.initials: L
authors.lastname: Blanc
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Michel
authors.initials: M
authors.lastname: Vidal
authors.forename: Joel Anne
authors.initials: JA
authors.lastname: Chasis
authors.forename: Xiuli
authors.initials: X
authors.lastname: An
authors.forename: Narla
authors.initials: N
authors.lastname: Mohandas
mesh_terms: D000818:Animals; D051398:Aquaporin 1 / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D048429:Cell Size; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D055354:Exosomes / Q000378:metabolism*; D007976:Leupeptins / Q000494:pharmacology; D051379:Mice; D009995:Osmosis / Q000187:drug effects / Q000502:physiology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D012156:Reticulocytes / Q000166:cytology / Q000378:metabolism*; D054875:Ubiquitination / Q000187:drug effects / Q000502:physiology*
chemical_list: C496021:Aqp1 protein, mouse; D015853:Cysteine Proteinase Inhibitors; D007976:Leupeptins; D061988:Proteasome Inhibitors; D051398:Aquaporin 1; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde