Analysis of the rainbow trout solute carrier 11 family reveals iron import ⩽ pH 7.4 and a functional isoform lacking transmembrane domains 11 and 12

Cooper, C; Shayeghi, Majid; Techau, Michala E; Capdevila, Davinia Morera; Mackenzie, Simon; Durrant, Chris; Bury, Nicolas R.

doi:10.1016/j.febslet.2007.04.081

Cited by 36 publications

(15 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One can speculate that these TM domains may (a) contribute additional functional determinants involved in regulation of transport, (b) provide docking sites for homo- or heterodimerization of the transporter or interaction with other proteins or other membrane constituents, or (c) provide structural determinants for stability and/or targeting to specific membrane microdomains. With respect to the latter point, we have previously shown that several sequence determinants downstream of TM12 at the C-terminus play an important role in targeting Slc11a1 and Slc11a2 to different endomembrane compartments and recycling from the plasma membrane via recycling endosomes (6,29,37). …”

Section: Discussionmentioning

confidence: 99%

Transmembrane Topology of the Mammalian Slc11a2 Iron Transporter

et al. 2009

View full text Add to dashboard Cite

The mammalian Slc11a1 and Slc11a2 proteins define a large family of secondary metal transporters. Slc11a1 and Slc11a2 function as pH-dependent divalent cation transporters that play a critical role in host defenses against infections and in Fe2+ homeostasis, respectively. The position and polarity of individual transmembrane domains (TMD) of Slc11a2 were studied by an epitope tagging method based on the insertion of small antigenic hemagglutinin A (HA) peptides (YPYDVPDYAS) in predicted intra- or extracellular loops of the protein. The tagged proteins were expressed in transfected LLC-PK1 kidney cells and tested for transport activity, and the polarity of inserted tags with respect to the plasma membrane was determined by immunofluorescence in intact and permeabilized cells. HA epitope tags were inserted at positions 1, 98, 131, 175, 201, 243, 284, 344, 403, 432, 468, 504, and 561. Insertions at positions 98, 131, 175, 403, and 432 abrogated metal transport by Slc11a2, while insertions at positions 1, 201, 243, 284, 344, 468, 504, and 561 resulted in functional proteins. Topology mapping in functional HA-tagged Slc11a2 proteins indicated that the N-terminus (1), as well as loops delineated by TMD4−5 (201), TMD6−7 (284), and TMD10−11 (468), and C-terminus (561) are intracellular, while loops separating TMD5−6 (243), TMD7−8 (344), and TMD11−12 (504) are extracellular. These results are compatible with a topology of 12 transmembrane domains, with intracellular amino and carboxy termini. Structural models constructed by homology threading support this 12TMD topology and show 2-fold structural symmetry in the arrangement of membrane helices for TM1−5 and TM6−10 (conserved Slc11 hydrophobic core).

show abstract

Section: Discussionmentioning

confidence: 99%

Transmembrane Topology of the Mammalian Slc11a2 Iron Transporter

et al. 2009

View full text Add to dashboard Cite

show abstract

“…These disparate observations may be the result of differences in Ni exposure concentration or species‐specific or tissue‐specific differences in DMT‐1 isoforms. For example, 2 different SLC11 isoforms have been isolated from rainbow trout gills for which Fe transport is differentially inhibited by various divalent metals (Ni was not studied) .…”

Section: Disruption Of Fe Homeostasismentioning

confidence: 99%

The mechanisms of nickel toxicity in aquatic environments: An adverse outcome pathway analysis

Brix

Schlekat²,

Garman³

2017

Enviro Toxic and Chemistry

View full text Add to dashboard Cite

Current ecological risk assessment and water quality regulations for nickel (Ni) use mechanistically based, predictive tools such as biotic ligand models (BLMs). However, despite many detailed studies, the precise mechanism(s) of Ni toxicity to aquatic organisms remains elusive. This uncertainty in the mechanism(s) of action for Ni has led to concern over the use of tools like the BLM in some regulatory settings. To address this knowledge gap, the authors used an adverse outcome pathway (AOP) analysis, the first AOP for a metal, to identify multiple potential mechanisms of Ni toxicity and their interactions with freshwater aquatic organisms. The analysis considered potential mechanisms of action based on data from a wide range of organisms in aquatic and terrestrial environments on the premise that molecular initiating events for an essential metal would potentially be conserved across taxa. Through this analysis the authors identified 5 potential molecular initiating events by which Ni may exert toxicity on aquatic organisms: disruption of Ca 2þ homeostasis, disruption of Mg 2þ homeostasis, disruption of Fe 2þ/3þ homeostasis, reactive oxygen species-induced oxidative damage, and an allergic-type response of respiratory epithelia. At the organ level of biological organization, these 5 potential molecular initiating events collapse into 3 potential pathways: reduced Ca 2þ availability to support formation of exoskeleton, shell, and bone for growth; impaired respiration; and cytotoxicity and tumor formation. At the level of the whole organism, the organ-level responses contribute to potential reductions in growth and reproduction and/or alterations in energy metabolism, with several potential feedback loops between each of the pathways. Overall, the present AOP analysis provides a robust framework for future directed studies on the mechanisms of Ni toxicity and for developing AOPs for other metals.

show abstract

“…NRAMP1 has been cloned in a number of fish species, including carp [ 139 ], fugu [ 140 ], channel catfish [ 141 ], rainbow trout [ 142 ], turbot [ 143 ], sea bream [ 144 ], Japanese flounder [ 145 ], and striped bass [ 144 ]. Although orthologs of Slc11 have been identified in several fish species, the phylogeny, sequence identities, and expression patterns of these teleost NRAMP orthologs do not clearly indicate whether these primordial counterparts are specifically orthologous to Slc11a1 or Slc11a2.…”

Section: Antimicrobial Roles Of Teleost M1 Macrophagesmentioning

confidence: 99%

Biology of Bony Fish Macrophages

Hodgkinson

Grayfer

Belosevic

2015

Biology

View full text Add to dashboard Cite

Macrophages are found across all vertebrate species, reside in virtually all animal tissues, and play critical roles in host protection and homeostasis. Various mechanisms determine and regulate the highly plastic functional phenotypes of macrophages, including antimicrobial host defenses (pro-inflammatory, M1-type), and resolution and repair functions (anti-inflammatory/regulatory, M2-type). The study of inflammatory macrophages in immune defense of teleosts has garnered much attention, and antimicrobial mechanisms of these cells have been extensively studied in various fish models. Intriguingly, both similarities and differences have been documented for the regulation of lower vertebrate macrophage antimicrobial defenses, as compared to what has been described in mammals. Advances in our understanding of the teleost macrophage M2 phenotypes likewise suggest functional conservation through similar and distinct regulatory strategies, compared to their mammalian counterparts. In this review, we discuss the current understanding of the molecular mechanisms governing teleost macrophage functional heterogeneity, including monopoetic development, classical macrophage inflammatory and antimicrobial responses as well as alternative macrophage polarization towards tissues repair and resolution of inflammation.

show abstract

Analysis of the rainbow trout solute carrier 11 family reveals iron import ⩽ pH 7.4 and a functional isoform lacking transmembrane domains 11 and 12

Cited by 36 publications

References 43 publications

Transmembrane Topology of the Mammalian Slc11a2 Iron Transporter

Transmembrane Topology of the Mammalian Slc11a2 Iron Transporter

The mechanisms of nickel toxicity in aquatic environments: An adverse outcome pathway analysis

Biology of Bony Fish Macrophages

Contact Info

Product

Resources

About