| First Author | Lanciotti A | Year | 2010 |
| Journal | Neurobiol Dis | Volume | 37 |
| Issue | 3 | Pages | 581-95 |
| PubMed ID | 19931615 | Mgi Jnum | J:180559 |
| Mgi Id | MGI:5306565 | Doi | 10.1016/j.nbd.2009.11.008 |
| Citation | Lanciotti A, et al. (2010) MLC1 trafficking and membrane expression in astrocytes: role of caveolin-1 and phosphorylation. Neurobiol Dis 37(3):581-95 |
| abstractText | 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. |
