Abstract
SNX-BAR proteins are a sub-family of sorting nexins implicated in endosomal sorting. Here, we establish that through its phox homology (PX) and Bin–Amphiphysin–Rvs (BAR) domains, sorting nexin-4 (SNX4) is associated with tubular and vesicular elements of a compartment that overlaps with peripheral early endosomes and the juxtanuclear endocytic recycling compartment (ERC). Suppression of SNX4 perturbs transport between these compartments and causes lysosomal degradation of the transferrin receptor (TfnR). Through an interaction with KIBRA, a protein previously shown to bind dynein light chain 1, we establish that SNX4 associates with the minus end-directed microtubule motor dynein. Although suppression of KIBRA and dynein perturbs early endosome-to-ERC transport, TfnR sorting is maintained. We propose that by driving membrane tubulation, SNX4 coordinates iterative, geometric-based sorting of the TfnR with the long-range transport of carriers from early endosomes to the ERC. Finally, these data suggest that by associating with molecular motors, SNX-BAR proteins may coordinate sorting with carrier transport between donor and recipient membranes.
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References
Maxfield, F. R. & McGraw, T. E. Endocytic recycling. Nature Rev. Mol. Cell Biol. 5, 121–132 (2004).
Gruenberg J. & Stenmark, H. The biogenesis of multivesicular endosomes. Nature Rev. Mol. Cell Biol. 5, 317–323 (2004).
Bonifacino, J. S. & Rojas, R. Retrograde transport from endosomes to the trans-Golgi network. Nature Rev. Mol. Cell Biol. 7, 568–579 (2006).
Slagsvold, T., Pattni, K., Malerod, L. & Stenmark, H. Endosomal and non-endosomal functions of ESCRT proteins. Trends Cell Biol. 16, 317–326 (2006).
van der Goot, G. & Gruenberg, J. Intra-endosomal membrane traffic. Trends Cell Biol. 16, 514–521 (2006).
Caviston, J. P. & Holzbaur, E. L. F. Microtubules motors at the intersection of trafficking and transport. Trends Cell Biol. 16, 530–537 (2006).
Soldati, T. & Schliwa, M. Powering membrane traffic in endocytosis and recycling. Nature Rev. Mol. Cell Biol. 7, 897–908 (2006).
Aniento, F., Emans, N., Griffths, G. & Gruenberg, J. Cytoplasmic dynein-dependent vesicular transport from early to late endosomes. J. Cell Biol. 123, 1373–1387 (1993).
Burkhardt, J. K., Echeverri, C. J., Nilsson, T. & Vallee, R. B. Overexpression of the dynamitin (p50) subunit of the dynactin complex disrupts dynein-dependent maintenance of membrane organelle distribution. J. Cell Biol. 139, 469–484 (1997).
Driskell, O. J., Mironov, A., Allan, V. J. & Woodman, P. G. Dynein is required for receptor sorting and the morphogenesis of early endosomes. Nature Cell Biol. 9, 113–120 (2007).
Hoepfner, S. et al. Modulation of receptor recycling and degradation by the endosomal kinesin KIF16B. Cell 121, 437–450 (2005).
Carlton, J. G., Bujny, M. V., Rutherford, A. & Cullen, P. J. Sorting nexins — unifying trends and new perspectives. Traffic 6, 75–82 (2005).
Pelham, H. R. B. Insights from yeast endosomes. Curr. Opin. Cell Biol. 14, 454–462 (2002).
Seaman, M. N. J. Recycling your receptors with retromer. Trends Cell Biol. 15, 68–75 (2005).
Arighi, C. N., Hartnell, L. M., Aguilar, R. C., Haft, C. R. & Bonifacino, J. S. Role of the mammalian retromer in sorting of the cation-independent mannose 6-phosphate receptor. J. Cell Biol. 165, 123–133 (2004).
Carlton, J. G. et al. Sorting nexin-1 mediates tubular endosome-to-TGN transport through co-incidence sensing of high curvature membranes and 3-phosphoinositides. Curr. Biol. 14, 1791–1800 (2004).
Seaman, M. N. J. Cargo-selective endosomal sorting for retrieval to the Golgi requires retromer. J. Cell Biol. 165, 111–122 (2004).
Chang, A. & Fink, G. R. Targeting of the yeast plasma membrane [H+]ATPase: a novel gene AST1 prevents mislocalization of mutant ATPase to the vacuole. J. Cell Biol. 128, 39–49 (1995).
Ekena, K. & Stevens, T. H. The Saccharomyces cerevisiae MVP1 gene interacts with VPS1 and is required for vacuolar protein sorting. Mol. Cell. Biol. 15, 1671–1678 (1995).
Hettema, E. H., Lewis, M. J., Black, M. W. & Pelham, H. R. B. Retromer and the sorting nexins Snx4/41/42 mediate distinct retrieval pathways from yeast endosomes. EMBO J. 22, 548–557 (2003).
Krsmanovic, T., Pawelec, A., Sydor, T. & Kolling, R. Control of Ste6 recycling by ubiquitination in the early endocytic pathway in yeast. Mol. Biol. Cell 16, 2809–2821 (2005).
Teasdale, R. D., Loci, D., Houghton, F., Karlsson, L. & Glesson, P. A. A large family of endosome-localised proteins related to sorting nexin-1. Biochem. J. 358, 7–16 (2001).
Leprince, C. et al. Sorting nexin-4 and amphiphysin 2, a new partnership between endocytosis and intracellular trafficking. J. Cell Sci. 116, 1937–1948 (2003).
Kremerskothen, J. et al. Characterisation of KIBRA, a novel WW domain-containing protein. Biochem. Biophys. Res. Commun. 300, 862–867 (2003).
Rayala, S. K. et al. Essential role of KIBRA in co-activator function of dynein light chain 1 in mammalian cells. J. Biol. Chem. 281, 19092–19099 (2006).
Papassotiropoulos, A. et al. Common Kibra alleles are associated with human memory performance. Science 314, 475–478 (2006).
Carlton, J. G. & Cullen, P. J. Co-incidence detection in phosphoinositide signalling. Trends Cell Biol. 15, 540–547 (2005).
Peter, B. J. et al. BAR domains as sensors of membrane curvature: the amphiphysin BAR structure. Science 303, 495–499 (2004).
Ikonomov, O. C. et al. Active PIKfyve associates with and promotes the membrane attachment of the late endosome-to-trans-Golgi network transport factor Rab9 effector p40. J. Biol. Chem. 278, 50863–50871 (2003).
Dove, S. K. et al. Svp1p defines a family of phosphatidylinositol 3,5-bisphosphate effectors. EMBO J. 23, 1922–1933 (2004).
Jeffries, T. R., Dove, S. K., Michell, R. H. & Parker, P. J. PtdIns-specific MPR pathway association of a novel WD40 repeat protein, WIPI49. Mol. Biol. Cell 15, 2652–2663 (2004).
Rutherford, A. C. et al. The mammalian phosphatidylinositol 3 monophosphate 5-kinase PIKfyve regulates endosome-to-TGN retrograde transport. J. Cell Sci. 119, 3944–3957 (2006).
Lundmark, R. & Carlsson, S. R. Regulated membrane recruitment of dynamin-2 mediated by sorting nexin-9. J. Biol. Chem. 279, 42694–42702 (2004).
Soulet, F., Yarar, D., Leonard, M. & Schmid, S. L. SNX9 regulates dynamin assembly and is required for efficient clathrin-mediated endocytosis. Mol. Biol. Cell 16, 2058–2067 (2005).
Roux, A., Cappello, G., Cartaud, J., Prost, J., Goud, B. & Bassereau, P. A minimal system allowing tubulation with molecular motors pulling on giant liposomes. Proc. Natl Acad. Sci. USA. 99, 5394–5399 (2002).
Dia, J. et al. ACAP1 promotes endocytic recycling by recognizing recycling sorting signals. Dev. Cell 7, 771–776 (2004).
Jing, S. Q., Spencer, T., Miller, K., Hopkins, C. R. & Trowbridge, I. S. Role of the human transferrin receptor cytoplasmic domain in endocytosis: localisation of a specific signal sequence for internalization. J. Cell Biol. 110, 283–294 (1990).
Johnson, L. S., Dunn, K. W., Pytowski, B. & McGraw, T. E. Endosome acidification and receptor trafficking: bafilomycin A1 shows receptor externalization by a mechanism involving the receptor's internalization motif. Mol. Biol. Cell 4, 1251–1266 (1993).
Dunn, K. W., McGraw, T. E. & Maxfield, F. R. Iterative fractionation of recycling receptors from lysosomally destined ligands in an early sorting endosome. J. Cell Biol. 109, 3303–3314 (1989).
Lane, J. D. et al. Caspase-mediated cleavage of the stacking protein GRASP65 is required for Golgi fragmentation during apoptosis. J. Cell Biol. 156, 495–509 (2002).
Watson, P. & Stephens, D. J. Microtubule plus-end loading of p150(Glued) is mediated by EB1 and CLIP-170 but is not required for intracellular membrane traffic in mammalian cells. J. Cell Sci. 119, 2758–2767 (2006).
Acknowledgements
This work was funded by the Wellcome Trust and a Medical Research Council Infrastructure Award (G4500006), which established the School of Medical Sciences Cell Imaging Facility. A.C.R was the recipient of a Medical Research Council Studentships. We thank M. Jepson and A. Leard for their assistance, J. Lane and M. McCaffrey for helpful discussion, and V. Hsu for ACAP1 constructs. D.J.S. is supported by the Medical Research Council through a Senior Research Fellowship.
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C.J.T., A.C.R., K.J.P., T.W., J.O., N.A. and J.G.C. contributed to experimental work, project planning, data analysis and manuscript writing. J.K. provided vital reagents and antibodies. D.J.S. and P.J.C. contributed to experimental work, project planning and manuscript writing.
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Traer, C., Rutherford, A., Palmer, K. et al. SNX4 coordinates endosomal sorting of TfnR with dynein-mediated transport into the endocytic recycling compartment. Nat Cell Biol 9, 1370–1380 (2007). https://doi.org/10.1038/ncb1656
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DOI: https://doi.org/10.1038/ncb1656
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