![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 15, Issue 5, 2143-2155, May 2004
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
* Department of Pharmacology, Cardiovascular Biology Center, Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7365;
Department of Genetics, Cardiovascular Biology Center, Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7365
Submitted September 30, 2003;
Revised January 22, 2004;
Accepted February 9, 2004
Monitoring Editor: Suzanne Pfeffer
Sorting nexin 1 (SNX1) and SNX2, homologues of the yeast vacuolar protein-sorting (Vps)5p, contain a phospholipid-binding motif termed the phox homology (PX) domain and a carboxyl terminal coiled-coil region. A role for SNX1 in trafficking of cell surface receptors from endosomes to lysosomes has been proposed; however, the function of SNX2 remains unknown. Toward understanding the function of SNX2, we first examined the distribution of endogenous protein in HeLa cells. We show that SNX2 resides primarily in early endosomes, whereas SNX1 is found partially in early endosomes and in tubulovesicular-like structures distributed throughout the cytoplasm. We also demonstrate that SNX1 interacts with the mammalian retromer complex through its amino terminal domain, whereas SNX2 does not. Moreover, activated endogenous epidermal growth factor receptor (EGFR) colocalizes markedly with SNX2-positive endosomes, but minimally with SNX1-containing vesicles. To assess SNX2 function, we examined the effect of a PX domain-mutated SNX2 that is defective in vesicle localization on EGFR trafficking. Mutant SNX2 markedly inhibited agonist-induced EGFR degradation, whereas internalization remained intact. In contrast, SNX1 PX domain mutants failed to effect EGFR degradation, whereas a SNX1 deletion mutant significantly inhibited receptor down-regulation. Interestingly, knockdown of SNX1 and SNX2 expression by RNA interference failed to alter agonist-induced EGFR down-regulation. Together, these findings suggest that both SNX1 and SNX2 are involved in regulating lysosomal sorting of internalized EGFR, but neither protein is essential for this process. These studies are the first to demonstrate a function for SNX2 in protein trafficking.
Abbreviations used: EEA1, early endosome antigen-1; EGFR, epidermal growth factor receptor; GFP, green fluorescent protein; LAMP1, lysosome-associated protein-1; PI, phosphoinositide; PX, phox homology; siRNA, small interfering RNA; SNX, sorting nexin; TfnR, transferrin receptor; TGN, trans-Golgi network, Vps, vacuolar protein-sorting.
These authors contributed equally to this work.
Present address: Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, FL 33612-9497.
|| Corresponding author. E-mail address: joann_trejo{at}med.unc.edu.
This article has been cited by other articles:
|
|
 |
|
  J. L. Fiori, T.-N. Zhu, M. P. O'Connell, K. S. Hoek, F. E. Indig, B. P. Frank, C. Morris, S. Kole, J. Hasskamp, G. Elias, et al. Filamin A Modulates Kinase Activation and Intracellular Trafficking of Epidermal Growth Factor Receptors in Human Melanoma Cells Endocrinology, June 1, 2009; 150(6): 2551 - 2560. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Katz, C. J. Evans, E. E. Heagney, P. A. vanKuyk, J. M. Kelly, and B. F. Cheetham Mutations in Genes Encoding Sorting Nexins Alter Production ofIntracellular and Extracellular Proteases in Aspergillus nidulans Genetics, April 1, 2009; 181(4): 1239 - 1247. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Rojas, T. van Vlijmen, G. A. Mardones, Y. Prabhu, A. L. Rojas, S. Mohammed, A. J.R. Heck, G. Raposo, P. van der Sluijs, and J. S. Bonifacino Regulation of retromer recruitment to endosomes by sequential action of Rab5 and Rab7 J. Cell Biol., November 3, 2008; 183(3): 513 - 526. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Cavet, J. Pang, G. Yin, and B. C. Berk An epidermal growth factor (EGF) -dependent interaction between GIT1 and sorting nexin 6 promotes degradation of the EGF receptor FASEB J, October 1, 2008; 22(10): 3607 - 3616. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Hara, E. Kiyokawa, S.-i. Iemura, T. Natsume, T. Wassmer, P. J. Cullen, H. Hiai, and M. Matsuda The DHR1 Domain of DOCK180 Binds to SNX5 and Regulates Cation-independent Mannose 6-phosphate Receptor Transport Mol. Biol. Cell, September 1, 2008; 19(9): 3823 - 3835. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. V. Bujny, V. Popoff, L. Johannes, and P. J. Cullen The retromer component sorting nexin-1 is required for efficient retrograde transport of Shiga toxin from early endosome to the trans Golgi network J. Cell Sci., June 15, 2007; 120(12): 2010 - 2021. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Rincon, T. Santos, A. Avila-Flores, J. P. Albar, V. Lalioti, C. Lei, W. Hong, and I. Merida Proteomics Identification of Sorting Nexin 27 as a Diacylglycerol Kinase {zeta}-associated Protein: New Diacylglycerol Kinase Roles in Endocytic Recycling Mol. Cell. Proteomics, June 1, 2007; 6(6): 1073 - 1087. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Rojas, S. Kametaka, C. R. Haft, and J. S. Bonifacino Interchangeable but Essential Functions of SNX1 and SNX2 in the Association of Retromer with Endosomes and the Trafficking of Mannose 6-Phosphate Receptors Mol. Cell. Biol., February 1, 2007; 27(3): 1112 - 1124. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Wassmer, N. Attar, M. V. Bujny, J. Oakley, C. J. Traer, and P. J. Cullen A loss-of-function screen reveals SNX5 and SNX6 as potential components of the mammalian retromer J. Cell Sci., January 1, 2007; 120(1): 45 - 54. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. N. Nguyen, M. S. Holdren, A. P. Nguyen, M. H. Furuya, M. Bianchini, E. Levy, J. Mordoh, A. Liu, G. D. Guncay, J. S. Campbell, et al. Sorting Nexin 1 Down-Regulation Promotes Colon Tumorigenesis Clin. Cancer Res., December 1, 2006; 12(23): 6952 - 6959. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Oliviusson, O. Heinzerling, S. Hillmer, G. Hinz, Y. C. Tse, L. Jiang, and D. G. Robinson Plant Retromer, Localized to the Prevacuolar Compartment and Microvesicles in Arabidopsis, May Interact with Vacuolar Sorting Receptors PLANT CELL, May 1, 2006; 18(5): 1239 - 1252. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Ren, P. Vajjhala, J. S. Lee, B. Winsor, and A. L. Munn The BAR Domain Proteins: Molding Membranes in Fission, Fusion, and Phagy Microbiol. Mol. Biol. Rev., March 1, 2006; 70(1): 37 - 120. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Gullapalli, B. L. Wolfe, C. T. Griffin, T. Magnuson, and J. Trejo An Essential Role for SNX1 in Lysosomal Sorting of Protease-activated Receptor-1: Evidence for Retromer-, Hrs-, and Tsg101-independent Functions of Sorting Nexins Mol. Biol. Cell, March 1, 2006; 17(3): 1228 - 1238. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Lindmo and H. Stenmark Regulation of membrane traffic by phosphoinositide 3-kinases J. Cell Sci., February 15, 2006; 119(4): 605 - 614. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Nakada-Tsukui, Y. Saito-Nakano, V. Ali, and T. Nozaki A Retromerlike Complex Is a Novel Rab7 Effector That Is Involved in the Transport of the Virulence Factor Cysteine Protease in the Enteric Protozoan Parasite Entamoeba histolytica Mol. Biol. Cell, November 1, 2005; 16(11): 5294 - 5303. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. T. Griffin, J. Trejo, and T. Magnuson Genetic evidence for a mammalian retromer complex containing sorting nexins 1 and 2 PNAS, October 18, 2005; 102(42): 15173 - 15177. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G. Carlton, M. V. Bujny, B. J. Peter, V. M. J. Oorschot, A. Rutherford, R. S. Arkell, J. Klumperman, H. T. McMahon, and P. J. Cullen Sorting nexin-2 is associated with tubular elements of the early endosome, but is not essential for retromer-mediated endosome-to-TGN transport J. Cell Sci., October 1, 2005; 118(19): 4527 - 4539. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Wang, M. Guo, Z. Liang, J. Fan, Z. Zhu, J. Zang, Z. Zhu, X. Li, M. Teng, L. Niu, et al. Crystal Structure of Human Vacuolar Protein Sorting Protein 29 Reveals a Phosphodiesterase/Nuclease-like Fold and Two Protein-Protein Interaction Sites J. Biol. Chem., June 17, 2005; 280(24): 22962 - 22967. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Zhong, M. J. Watson, C. S. Lazar, A. M. Hounslow, J. P. Waltho, and G. N. Gill Determinants of the Endosomal Localization of Sorting Nexin 1 Mol. Biol. Cell, April 1, 2005; 16(4): 2049 - 2057. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Stalheim, Y. Ding, A. Gullapalli, M. M. Paing, B. L. Wolfe, D. R. Morris, and J. Trejo Multiple Independent Functions of Arrestins in the Regulation of Protease-Activated Receptor-2 Signaling and Trafficking Mol. Pharmacol., January 1, 2005; 67(1): 78 - 87. [Abstract] [Full Text] [PDF]
|
|
