RGD Reference Report - MLC1 trafficking and membrane expression in astrocytes: role of caveolin-1 and phosphorylation. - Rat Genome Database

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MLC1 trafficking and membrane expression in astrocytes: role of caveolin-1 and phosphorylation.

Authors: Lanciotti, A  Brignone, MS  Camerini, S  Serafini, B  Macchia, G  Raggi, C  Molinari, P  Crescenzi, M  Musumeci, M  Sargiacomo, M  Aloisi, F  Petrucci, TC  Ambrosini, E 
Citation: Lanciotti A, etal., Neurobiol Dis. 2010 Mar;37(3):581-95. Epub 2009 Nov 26.
RGD ID: 2326037
Pubmed: PMID:19931615   (View Abstract at PubMed)
DOI: DOI:10.1016/j.nbd.2009.11.008   (Journal Full-text)

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare congenital leukodystrophy caused by mutations in the MLC1 gene that encodes a membrane protein of unknown function. In the brain MLC1 protein is mainly expressed in astrocyte end-feet, localizes in lipid rafts and associates with the dystrophin glycoprotein complex (DGC). Using pull-down and co-fractionation assays in cultured human and rat astrocytes, we show here that MLC1 intracellular domains pull-down the DGC proteins syntrophin, dystrobrevin, Kir4.1 and caveolin-1, the structural protein of caveolae, thereby supporting a role for DGC and caveolar structures in MLC1 function. By immunostaining and subcellular fractionation of cultured rat or human astrocytes treated with agents modulating caveolin-mediated trafficking, we demonstrate that MLC1 is also expressed in intracellular vesicles and endoplasmic reticulum and undergoes caveolae/raft-mediated endocytosis. Inhibition of endocytosis, cholesterol lowering and protein kinases A- and C-mediated MLC1 phosphorylation favour the expression of membrane-associated MLC1. Because pathological mutations prevent MLC1 membrane expression, the identification of substances regulating MLC1 intracellular trafficking is potentially relevant for the therapy of MLC.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Mlc1Ratcaveolin-mediated endocytosis involved_inIMP PMID:19931615UniProt 
Mlc1Ratcellular response to cholesterol involved_inIDA PMID:19931615UniProt 
Mlc1Ratprotein transport involved_inIDA PMID:19931615UniProt 
Mlc1Ratvesicle-mediated transport involved_inIDA PMID:19931615UniProt 

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Cav1Ratcaveola located_inIDA PMID:19931615UniProt 
Mlc1Ratcaveola located_inIDA PMID:19931615UniProt 
Mlc1Ratclathrin-coated vesicle NOT|located_inIDA PMID:19931615UniProt 
Mlc1Ratcytoplasmic vesicle located_inIDA PMID:19931615UniProt 
Mlc1Ratearly endosome located_inIDA PMID:19931615UniProt 
Mlc1Ratendoplasmic reticulum located_inIDA PMID:19931615UniProt 
Mlc1Ratlysosome located_inIDA PMID:19931615UniProt 
Mlc1Ratmembrane raft located_inIDA PMID:19931615UniProt 
Cav1Ratperinuclear region of cytoplasm located_inIDA PMID:19931615UniProt 
Mlc1Ratperinuclear region of cytoplasm  IDA  RGD 
Mlc1Ratplasma membrane located_inIDA PMID:19931615UniProt 
Mlc1Ratrecycling endosome located_inIDA PMID:19931615UniProt 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
DtnaRatprotein binding enablesIPIUniProtKB:Q15049PMID:19931615UniProt 
Kcnj10Ratprotein binding enablesIPIUniProtKB:Q15049PMID:19931615UniProt 
Kcnj10Ratprotein binding  IPIMLC1 (Homo sapiens) RGD 
Tuba1aRatprotein binding enablesIPIUniProtKB:Q15049PMID:19931615UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Cav1  (caveolin 1)
Dtna  (dystrobrevin, alpha)
Kcnj10  (potassium inwardly-rectifying channel, subfamily J, member 10)
Mlc1  (modulator of VRAC current 1)
Tuba1a  (tubulin, alpha 1A)

Objects referenced in this article
Gene Snta1 syntrophin, alpha 1 Rattus norvegicus

Additional Information