The lysosomal transporter MFSD1 is essential for liver homeostasis and critically depends on its accessory subunit GLMP.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31661432.
- Also identified by DOI 10.7554/eLife.50025 and PMC identifier 6819133.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Lysosomes are major sites for intracellular, acidic hydrolase-mediated proteolysis and cellular degradation. The export of low-molecular-weight catabolic end-products is facilitated by polytopic transmembrane proteins mediating secondary active or passive transport. A number of these lysosomal transporters, however, remain enigmatic. We present a detailed analysis of MFSD1, a hitherto uncharacterized lysosomal family member of the major facilitator superfamily. MFSD1 is not N-glycosylated. It contains a dileucine-based sorting motif needed for its transport to lysosomes. <i>Mfsd1</i> knockout mice develop splenomegaly and severe liver disease. Proteomics of isolated lysosomes from <i>Mfsd1</i> knockout mice revealed GLMP as a critical accessory subunit for MFSD1. MFSD1 and GLMP physically interact. GLMP is essential for the maintenance of normal levels of MFSD1 in lysosomes and vice versa. <i>Glmp</i> knockout mice mimic the phenotype of <i>Mfsd1</i> knockout mice. Our data reveal a tightly linked MFSD1/GLMP lysosomal membrane protein transporter complex.
Medical subject headings
- Liver
- Lysosomes
- Membrane Proteins
- Membrane Transport Proteins