Hrs and SNX3 functions in sorting and membrane invagination within multivesicular bodies

Véronique Pons; Pierre-Philippe Luyet; Etienne Morel; Laurence Abrami; F Gisou van der Goot; Robert G Parton; Jean Gruenberg

doi:10.1371/journal.pbio.0060214

Hrs and SNX3 functions in sorting and membrane invagination within multivesicular bodies

PLoS Biol. 2008 Sep 2;6(9):e214. doi: 10.1371/journal.pbio.0060214.

Authors

Véronique Pons¹, Pierre-Philippe Luyet, Etienne Morel, Laurence Abrami, F Gisou van der Goot, Robert G Parton, Jean Gruenberg

Affiliation

¹ Department of Biochemistry, University of Geneva, Geneva, Switzerland.

Abstract

After internalization, ubiquitinated signaling receptors are delivered to early endosomes. There, they are sorted and incorporated into the intralumenal invaginations of nascent multivesicular bodies, which function as transport intermediates to late endosomes. Receptor sorting is achieved by Hrs--an adaptor--like protein that binds membrane PtdIns3P via a FYVE motif-and then by ESCRT complexes, which presumably also mediate the invagination process. Eventually, intralumenal vesicles are delivered to lysosomes, leading to the notion that EGF receptor sorting into multivesicular bodies mediates lysosomal targeting. Here, we report that Hrs is essential for lysosomal targeting but dispensable for multivesicular body biogenesis and transport to late endosomes. By contrast, we find that the PtdIns3P-binding protein SNX3 is required for multivesicular body formation, but not for EGF receptor degradation. PtdIns3P thus controls the complementary functions of Hrs and SNX3 in sorting and multivesicular body biogenesis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Membrane / metabolism*
Endocytosis / physiology*
Endosomal Sorting Complexes Required for Transport
Endosomes / metabolism*
Epidermal Growth Factor / metabolism
ErbB Receptors / genetics
ErbB Receptors / metabolism
HeLa Cells
Humans
Lysosomal Membrane Proteins / genetics
Lysosomal Membrane Proteins / metabolism
Lysosomes / metabolism*
Phosphatidylinositol Phosphates / metabolism
Phosphoproteins / genetics
Phosphoproteins / metabolism*
Protein Transport / physiology
Recombinant Fusion Proteins / genetics
Recombinant Fusion Proteins / metabolism
Sorting Nexins
Ubiquitin / metabolism
Vesicular Transport Proteins / genetics
Vesicular Transport Proteins / metabolism*
rab5 GTP-Binding Proteins / genetics
rab5 GTP-Binding Proteins / metabolism

Substances

Endosomal Sorting Complexes Required for Transport
LAMP1 protein, human
Lysosomal Membrane Proteins
Phosphatidylinositol Phosphates
Phosphoproteins
Recombinant Fusion Proteins
SNX3 protein, human
Sorting Nexins
Ubiquitin
Vesicular Transport Proteins
early endosome antigen 1
hepatocyte growth factor-regulated tyrosine kinase substrate
phosphatidylinositol 3-phosphate
Epidermal Growth Factor
ErbB Receptors
rab5 GTP-Binding Proteins