Matches in SemOpenAlex for { <https://semopenalex.org/work/W2092166138> ?p ?o ?g. }
Showing items 1 to 93 of
93
with 100 items per page.
- W2092166138 endingPage "266a" @default.
- W2092166138 startingPage "266a" @default.
- W2092166138 abstract "TRPML1 (mucolipin-1/MCOLN1) is predicted to be an intracellular late endosomal and lysosomal ion channel protein belonging to the mucolipin subfamily of Transient Receptor Potential (TRP) proteins. Mutations in the human TRPML1 gene cause mucolipidosis type IV disease (ML4). ML4 patients exhibit motor impairment, mental retardation, retinal degeneration, and iron-deficiency anemia. Since aberrant iron metabolism may cause neural and retinal degeneration, it may be a primary cause of ML4 phenotypes. In most mammalian cells, release of iron from endosomes and lysosomes following iron uptake via endocytosis of Fe3+-bound transferrin receptors, or following lysosomal degradation of ferritin-Fe complexes and autophagic ingestion of iron-containing macromolecules, is the major source of cellular iron. The Divalent Metal Transporter protein (DMT1) is the only endosomal Fe2+ transporter currently known and is highly expressed in erythroid precursors, but genetic studies suggest the existence of a DMT1-independent endosomal/lysosomal Fe2+ transport protein. Here, by measuring radiolabeled iron uptake, monitoring the levels of cytosolic and intra-lysosomal iron and directly patch-clamping the late endosomal/lysosomal membrane, we show that TRPML1 functions as a Fe2+ permeable channel in late endosomes and lysosomes. ML4 mutations are shown to impair TRPML1's ability to permeate Fe2+ at varying degrees, which correlate well with the disease severity. A comparison of TRPML1−/− ML4 and control skin fibroblasts showed a reduction of cytosolic Fe2+ levels, an increase of intra-lysosomal Fe2+ levels, and an accumulation of lipofuscin-like molecules in TRPML1−/− cells. We propose that TRPML1 mediates a mechanism by which Fe2+ is released from late endosomes/lysosomes. Our results suggest that impaired iron transport may contribute to both hematological and degenerative symptoms of ML4 patients." @default.
- W2092166138 created "2016-06-24" @default.
- W2092166138 creator A5015982143 @default.
- W2092166138 creator A5031320671 @default.
- W2092166138 creator A5040902469 @default.
- W2092166138 creator A5069551145 @default.
- W2092166138 creator A5074294571 @default.
- W2092166138 creator A5083516558 @default.
- W2092166138 creator A5086060042 @default.
- W2092166138 date "2009-02-01" @default.
- W2092166138 modified "2023-09-25" @default.
- W2092166138 title "The Type IV Mucolipidosis-Associated Protein TRPML1 is an Endolysosomal Iron Release Channel" @default.
- W2092166138 doi "https://doi.org/10.1016/j.bpj.2008.12.1314" @default.
- W2092166138 hasPublicationYear "2009" @default.
- W2092166138 type Work @default.
- W2092166138 sameAs 2092166138 @default.
- W2092166138 citedByCount "0" @default.
- W2092166138 crossrefType "journal-article" @default.
- W2092166138 hasAuthorship W2092166138A5015982143 @default.
- W2092166138 hasAuthorship W2092166138A5031320671 @default.
- W2092166138 hasAuthorship W2092166138A5040902469 @default.
- W2092166138 hasAuthorship W2092166138A5069551145 @default.
- W2092166138 hasAuthorship W2092166138A5074294571 @default.
- W2092166138 hasAuthorship W2092166138A5083516558 @default.
- W2092166138 hasAuthorship W2092166138A5086060042 @default.
- W2092166138 hasBestOaLocation W20921661381 @default.
- W2092166138 hasConcept C102747710 @default.
- W2092166138 hasConcept C104317684 @default.
- W2092166138 hasConcept C149011108 @default.
- W2092166138 hasConcept C155164980 @default.
- W2092166138 hasConcept C170493617 @default.
- W2092166138 hasConcept C181199279 @default.
- W2092166138 hasConcept C185592680 @default.
- W2092166138 hasConcept C22814914 @default.
- W2092166138 hasConcept C2776531687 @default.
- W2092166138 hasConcept C2778264360 @default.
- W2092166138 hasConcept C2780216420 @default.
- W2092166138 hasConcept C2780905385 @default.
- W2092166138 hasConcept C32264632 @default.
- W2092166138 hasConcept C55493867 @default.
- W2092166138 hasConcept C57581600 @default.
- W2092166138 hasConcept C79879829 @default.
- W2092166138 hasConcept C86803240 @default.
- W2092166138 hasConcept C95444343 @default.
- W2092166138 hasConceptScore W2092166138C102747710 @default.
- W2092166138 hasConceptScore W2092166138C104317684 @default.
- W2092166138 hasConceptScore W2092166138C149011108 @default.
- W2092166138 hasConceptScore W2092166138C155164980 @default.
- W2092166138 hasConceptScore W2092166138C170493617 @default.
- W2092166138 hasConceptScore W2092166138C181199279 @default.
- W2092166138 hasConceptScore W2092166138C185592680 @default.
- W2092166138 hasConceptScore W2092166138C22814914 @default.
- W2092166138 hasConceptScore W2092166138C2776531687 @default.
- W2092166138 hasConceptScore W2092166138C2778264360 @default.
- W2092166138 hasConceptScore W2092166138C2780216420 @default.
- W2092166138 hasConceptScore W2092166138C2780905385 @default.
- W2092166138 hasConceptScore W2092166138C32264632 @default.
- W2092166138 hasConceptScore W2092166138C55493867 @default.
- W2092166138 hasConceptScore W2092166138C57581600 @default.
- W2092166138 hasConceptScore W2092166138C79879829 @default.
- W2092166138 hasConceptScore W2092166138C86803240 @default.
- W2092166138 hasConceptScore W2092166138C95444343 @default.
- W2092166138 hasIssue "3" @default.
- W2092166138 hasLocation W20921661381 @default.
- W2092166138 hasOpenAccess W2092166138 @default.
- W2092166138 hasPrimaryLocation W20921661381 @default.
- W2092166138 hasRelatedWork W180602949 @default.
- W2092166138 hasRelatedWork W1969515779 @default.
- W2092166138 hasRelatedWork W1979436212 @default.
- W2092166138 hasRelatedWork W2003691303 @default.
- W2092166138 hasRelatedWork W2017011727 @default.
- W2092166138 hasRelatedWork W2022982095 @default.
- W2092166138 hasRelatedWork W2027522832 @default.
- W2092166138 hasRelatedWork W2040731722 @default.
- W2092166138 hasRelatedWork W2087320761 @default.
- W2092166138 hasRelatedWork W2092623477 @default.
- W2092166138 hasRelatedWork W2118417727 @default.
- W2092166138 hasRelatedWork W2120643929 @default.
- W2092166138 hasRelatedWork W2153622855 @default.
- W2092166138 hasRelatedWork W2165500244 @default.
- W2092166138 hasRelatedWork W2316605381 @default.
- W2092166138 hasRelatedWork W2595479073 @default.
- W2092166138 hasRelatedWork W2762908328 @default.
- W2092166138 hasRelatedWork W2904349367 @default.
- W2092166138 hasRelatedWork W2998575086 @default.
- W2092166138 hasRelatedWork W3179581347 @default.
- W2092166138 hasVolume "96" @default.
- W2092166138 isParatext "false" @default.
- W2092166138 isRetracted "false" @default.
- W2092166138 magId "2092166138" @default.
- W2092166138 workType "article" @default.