The PX-domain protein SNX17 interacts with members of the LDL receptor family and modulates endocytosis of the LDL receptor.
Sorting nexins (SNXs) comprise a family of proteins characterized by the presence of a phox-homology domain, which mediates the association of these proteins with phosphoinositides and recruits them to specific membranes or vesicular structures within cells. Although only limited information about SNXs and their functions is available, they seem to be involved in membrane trafficking and sorting processes by directly binding to target proteins such as certain growth factor receptors. We show that SNX17 binds to the intracellular domain of some members of the low-density lipoprotein receptor (LDLR) family such as LDLR, VLDLR, ApoER2 and LDLR-related protein. SNX17 resides on distinct vesicular structures partially overlapping with endosomal compartments characterized by the presence of EEA1 and rab4. Using rhodamine-labeled LDL, it was possible to demonstrate that during endocytosis, LDL passes through SNX17-positive compartments. Functional studies on the LDLR pathway showed that SNX17 enhances the endocytosis rate of this receptor. Our results identify SNX17 as a novel adaptor protein for LDLR family members and define a novel mechanism for modulation of their endocytic activity.
Stockinger
Walter
W
The Institute of Medical Biochemistry, Department of Molecular Genetics, BioCenter and University of Vienna, A-1030 Vienna, Austria.
Sailler
Beate
B
Strasser
Vera
V
Recheis
Burgi
B
Fasching
Daniela
D
Kahr
Larissa
L
Schneider
Wolfgang J
WJ
Nimpf
Johannes
J
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004705:Endocytosis / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D026502:LDL-Receptor Related Proteins; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011973:Receptors, LDL / Q000378:metabolism*; D018110:Receptors, Lipoprotein / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D058305:Sorting Nexins; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; C103773:Dab1 protein, mouse; D026502:LDL-Receptor Related Proteins; D026561:Low Density Lipoprotein Receptor-Related Protein-2; D009419:Nerve Tissue Proteins; D011973:Receptors, LDL; D018110:Receptors, Lipoprotein; D011994:Recombinant Proteins; C465498:Snx17 protein, mouse; D058305:Sorting Nexins; D033921:Vesicular Transport Proteins; C098773:low density lipoprotein receptor-related protein 8