Molecular mechanism to recruit galectin-3 into multivesicular bodies for polarized exosomal secretion.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29686075.
- Also identified by DOI 10.1073/pnas.1718921115 and PMC identifier 5948969.
- No licence information is recorded for this record.
- Because redistribution is not established, this page shows the abstract only. Follow the links below for the full text.
Abstract
The beta-galactoside binding lectin galectin-3 (Gal3) is found intracellularly and in the extracellular space. Secretion of this lectin is mediated independently of the secretory pathway by a not yet defined nonclassical mechanism. Here, we found Gal3 in the lumen of exosomes. Superresolution and electron microscopy studies visualized Gal3 recruitment and sorting into intraluminal vesicles. Exosomal Gal3 release depends on the endosomal sorting complex required for transport I (ESCRT-I) component Tsg101 and functional Vps4a. Either Tsg101 knockdown or expression of dominant-negative Vps4a<sup>E228Q</sup> causes an intracellular Gal3 accumulation at multivesicular body formation sites. In addition, we identified a highly conserved tetrapeptide P(S/T)AP motif in the amino terminus of Gal3 that mediates a direct interaction with Tsg101. Mutation of the P(S/T)AP motif results in a loss of interaction and a dramatic decrease in exosomal Gal3 secretion. We conclude that Gal3 is a member of endogenous non-ESCRT proteins which are P(S/T)AP tagged for exosomal release.
Medical subject headings
- DNA-Binding Proteins
- Endosomal Sorting Complexes Required for Transport
- Endosomes
- Exosomes
- Galectin 3
- Multivesicular Bodies
- Transcription Factors
- Vacuolar Proton-Translocating ATPases