Receptor-mediated Endocytosis 8 Utilizes an N-terminal Phosphoinositide-binding Motif to Regulate Endosomal Clathrin Dynamics

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2015 Jul 3

PMID 26134565

Citations 12

Authors

Besa Xhabija

Panayiotis O Vacratsis

Affiliations

Soon will be listed here.

Abstract

Receptor-mediated endocytosis 8 (RME-8) is a DnaJ domain containing protein implicated in translocation of Hsc70 to early endosomes for clathrin removal during retrograde transport. Previously, we have demonstrated that RME-8 associates with early endosomes in a phosphatidylinositol 3-phosphate (PI(3)P)-dependent fashion. In this study, we have now identified amino acid determinants required for PI(3)P binding within a region predicted to adopt a pleckstrin homology-like fold in the N terminus of RME-8. The ability of RME-8 to associate with PI(3)P and early endosomes is largely abolished when residues Lys(17), Trp(20), Tyr(24), or Arg(26) are mutated resulting in diffuse cytoplasmic localization of RME-8 while maintaining the ability to interact with Hsc70. We also provide evidence that RME-8 PI(3)P binding regulates early endosomal clathrin dynamics and alters the steady state localization of the cation-independent mannose 6-phosphate receptor. Interestingly, RME-8 endosomal association is also regulated by the PI(3)P-binding protein SNX1, a member of the retromer complex. Wild type SNX1 restores endosomal localization of RME-8 W20A, whereas a SNX1 variant deficient in PI(3)P binding disrupts endosomal localization of wild type RME-8. These results further highlight the critical role for PI(3)P in the RME-8-mediated organizational control of various endosomal activities, including retrograde transport.

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References

Bolte S, Cordelieres F . A guided tour into subcellular colocalization analysis in light microscopy. J Microsc. 2007; 224(Pt 3):213-32. DOI: 10.1111/j.1365-2818.2006.01706.x. View

Saltel F, Mortier E, Hytonen V, Jacquier M, Zimmermann P, Vogel V . New PI(4,5)P2- and membrane proximal integrin-binding motifs in the talin head control beta3-integrin clustering. J Cell Biol. 2009; 187(5):715-31. PMC: 2806581. DOI: 10.1083/jcb.200908134. View

Kiefer F, Arnold K, Kunzli M, Bordoli L, Schwede T . The SWISS-MODEL Repository and associated resources. Nucleic Acids Res. 2008; 37(Database issue):D387-92. PMC: 2686475. DOI: 10.1093/nar/gkn750. View

Eisenberg E, Greene L . Multiple roles of auxilin and hsc70 in clathrin-mediated endocytosis. Traffic. 2007; 8(6):640-6. DOI: 10.1111/j.1600-0854.2007.00568.x. View

Kelley L, Sternberg M . Protein structure prediction on the Web: a case study using the Phyre server. Nat Protoc. 2009; 4(3):363-71. DOI: 10.1038/nprot.2009.2. View

Brodsky F, Chen C, Knuehl C, Towler M, Wakeham D . Biological basket weaving: formation and function of clathrin-coated vesicles. Annu Rev Cell Dev Biol. 2001; 17:517-68. DOI: 10.1146/annurev.cellbio.17.1.517. View

Zhong Q, Lazar C, Tronchere H, Sato T, Meerloo T, Yeo M . Endosomal localization and function of sorting nexin 1. Proc Natl Acad Sci U S A. 2002; 99(10):6767-72. PMC: 124477. DOI: 10.1073/pnas.092142699. View

Lemmon M . Membrane recognition by phospholipid-binding domains. Nat Rev Mol Cell Biol. 2008; 9(2):99-111. DOI: 10.1038/nrm2328. View

Kelley L, Mezulis S, Yates C, Wass M, Sternberg M . The Phyre2 web portal for protein modeling, prediction and analysis. Nat Protoc. 2015; 10(6):845-58. PMC: 5298202. DOI: 10.1038/nprot.2015.053. View

10.

Klumperman J, Hille A, Veenendaal T, Oorschot V, Stoorvogel W, von Figura K . Differences in the endosomal distributions of the two mannose 6-phosphate receptors. J Cell Biol. 1993; 121(5):997-1010. PMC: 2119677. DOI: 10.1083/jcb.121.5.997. View

11.

Popoff V, Mardones G, Tenza D, Rojas R, Lamaze C, Bonifacino J . The retromer complex and clathrin define an early endosomal retrograde exit site. J Cell Sci. 2007; 120(Pt 12):2022-31. DOI: 10.1242/jcs.003020. View

12.

Bonifacino J, Hurley J . Retromer. Curr Opin Cell Biol. 2008; 20(4):427-36. PMC: 2833274. DOI: 10.1016/j.ceb.2008.03.009. View

13.

Cozier G, Carlton J, McGregor A, Gleeson P, Teasdale R, Mellor H . The phox homology (PX) domain-dependent, 3-phosphoinositide-mediated association of sorting nexin-1 with an early sorting endosomal compartment is required for its ability to regulate epidermal growth factor receptor degradation. J Biol Chem. 2002; 277(50):48730-6. DOI: 10.1074/jbc.M206986200. View

14.

Shi A, Sun L, Banerjee R, Tobin M, Zhang Y, Grant B . Regulation of endosomal clathrin and retromer-mediated endosome to Golgi retrograde transport by the J-domain protein RME-8. EMBO J. 2009; 28(21):3290-302. PMC: 2776105. DOI: 10.1038/emboj.2009.272. View

15.

Vilarino-Guell C, Rajput A, Milnerwood A, Shah B, Szu-Tu C, Trinh J . DNAJC13 mutations in Parkinson disease. Hum Mol Genet. 2013; 23(7):1794-801. PMC: 3999380. DOI: 10.1093/hmg/ddt570. View

16.

Martel V, Racaud-Sultan C, Dupe S, Marie C, Paulhe F, Galmiche A . Conformation, localization, and integrin binding of talin depend on its interaction with phosphoinositides. J Biol Chem. 2001; 276(24):21217-27. DOI: 10.1074/jbc.M102373200. View

17.

Scheele U, Alves J, Frank R, Duwel M, Kalthoff C, Ungewickell E . Molecular and functional characterization of clathrin- and AP-2-binding determinants within a disordered domain of auxilin. J Biol Chem. 2003; 278(28):25357-68. DOI: 10.1074/jbc.M303738200. View

18.

Ungewickell E, Ungewickell H, Holstein S, Lindner R, Prasad K, Barouch W . Role of auxilin in uncoating clathrin-coated vesicles. Nature. 1995; 378(6557):632-5. DOI: 10.1038/378632a0. View

19.

Brodin L, Low P, Shupliakov O . Sequential steps in clathrin-mediated synaptic vesicle endocytosis. Curr Opin Neurobiol. 2000; 10(3):312-20. DOI: 10.1016/s0959-4388(00)00097-0. View

20.

Chenna R, Sugawara H, Koike T, Lopez R, Gibson T, Higgins D . Multiple sequence alignment with the Clustal series of programs. Nucleic Acids Res. 2003; 31(13):3497-500. PMC: 168907. DOI: 10.1093/nar/gkg500. View