SNX12 role in endosome membrane transport.
In this paper, we investigated the role of sorting nexin 12 (SNX12) in the endocytic pathway. SNX12 is a member of the PX domain-containing sorting nexin family and shares high homology with SNX3, which plays a central role in the formation of intralumenal vesicles within multivesicular endosomes. We found that SNX12 is expressed at very low levels compared to SNX3. SNX12 is primarily associated with early endosomes and this endosomal localization depends on the binding to 3-phosphoinositides. We find that overexpression of SNX12 prevents the detachment (or maturation) of multivesicular endosomes from early endosomes. This in turn inhibits the degradative pathway from early to late endosomes/lysosomes, much like SNX3 overexpression, without affecting endocytosis, recycling and retrograde transport. In addition, while previous studies showed that Hrs knockdown prevents EGF receptor sorting into multivesicular endosomes, we find that overexpression of SNX12 restores the sorting process in an Hrs knockdown background. Altogether, our data show that despite lower expression level, SNX12 shares redundant functions with SNX3 in the biogenesis of multivesicular endosomes.
Department of Biochemistry, University of Geneva, Geneva, Switzerland.
Véronique
V
Pons
Cansel
C
Ustunel
Corinne
C
Rolland
Eleonora
E
Torti
Robert G
RG
Parton
Jean
J
Gruenberg
D000595:Amino Acid Sequence; D001483:Base Sequence; D045744:Cell Line, Tumor; D017931:DNA Primers; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D021381:Protein Transport; D034622:RNA Interference; D017386:Sequence Homology, Amino Acid; D058305:Sorting Nexins / Q000502:physiology*; D018116:Vesiculovirus / Q000502:physiology
D017931:DNA Primers; D008565:Membrane Proteins; C576724:SNX12 protein, human; D058305:Sorting Nexins