title: Leishmania donovani amastigotes mobilize organic and inorganic osmolytes during regulatory volume decrease.
abstract: The protozoan parasite Leishmania donovani encounters large fluctuations in osmolality as it cycles between its insect vector and human host. The flagellated promastigote exhibits regulatory volume responses involving organic and inorganic osmolytes, but little is known about volume regulation in the clinically relevant amastigote that multiplies within the parasitophorous vacuoles of mammalian host cells. Using a combination of morphological, X-ray microanalytical, and biochemical approaches we determined that non-motile amastigotes respond to hypotonic stress with (1) an amino acid and l-alanine-mediated regulatory volume decrease, and (2) a parallel release of Na+, K+, P (presumably as negatively charged phosphates), and subsequently Cl- from cytoplasm and the cell as a whole. In addition P, Zn2+, and subsequently Ca2+ increase in acidocalcisomes as Cl- content declines in this compartment. This evidence is the first to document subcellular translocation of, and thus a potential role for, zinc in volume regulatory responses. These coordinated changes in organic and inorganic osmolytes demonstrate that amastigote subcellular compartments, particularly acidocalcisomes, function in maintaining ionic homeostasis in the response of Leishmania amastigotes to hypo-osmotic stress.
authors.affiliation: Durham Veterans Affairs Medical Center, Duke University Medical Center, Durham, NC 27705, USA. a.lefurgey@cellbio.duke.edu
authors.forename: Ann
authors.initials: A
authors.lastname: Lefurgey
authors.forename: Melissa
authors.initials: M
authors.lastname: Gannon
authors.forename: Joseph
authors.initials: J
authors.lastname: Blum
authors.forename: Peter
authors.initials: P
authors.lastname: Ingram
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002713:Chlorine / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism; D007893:Leishmania donovani / Q000502:physiology* / Q000648:ultrastructure; D010758:Phosphorus / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D014882:Water-Electrolyte Balance / Q000502:physiology; D015032:Zinc / Q000378:metabolism
chemical_list: D010758:Phosphorus; D002713:Chlorine; D012964:Sodium; D015032:Zinc; D011188:Potassium; D002118:Calcium