The Fifth Adaptor Protein Complex

Overview

Journal PLoS Biol

Specialty Biology

Date 2011 Oct 25

PMID 22022230

Citations 151

Authors

Jennifer Hirst

Lael D Barlow

Gabriel Casey Francisco

Daniela A Sahlender

Matthew N J Seaman

Joel B Dacks

Margaret S Robinson

Affiliations

Soon will be listed here.

Abstract

Adaptor protein (AP) complexes sort cargo into vesicles for transport from one membrane compartment of the cell to another. Four distinct AP complexes have been identified, which are present in most eukaryotes. We report the existence of a fifth AP complex, AP-5. Tagged AP-5 localises to a late endosomal compartment in HeLa cells. AP-5 does not associate with clathrin and is insensitive to brefeldin A. Knocking down AP-5 subunits interferes with the trafficking of the cation-independent mannose 6-phosphate receptor and causes the cell to form swollen endosomal structures with emanating tubules. AP-5 subunits can be found in all five eukaryotic supergroups, but they have been co-ordinately lost in many organisms. Concatenated phylogenetic analysis provides robust resolution, for the first time, into the evolutionary order of emergence of the adaptor subunit families, showing AP-3 as the basal complex, followed by AP-5, AP-4, and AP-1 and AP-2. Thus, AP-5 is an evolutionarily ancient complex, which is involved in endosomal sorting, and which has links with hereditary spastic paraplegia.

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References

Heldwein E, Macia E, Wang J, Yin H, Kirchhausen T, Harrison S . Crystal structure of the clathrin adaptor protein 1 core. Proc Natl Acad Sci U S A. 2004; 101(39):14108-13. PMC: 521094. DOI: 10.1073/pnas.0406102101. View

Abascal F, Zardoya R, Posada D . ProtTest: selection of best-fit models of protein evolution. Bioinformatics. 2005; 21(9):2104-5. DOI: 10.1093/bioinformatics/bti263. View

DellAngelica E, Shotelersuk V, Aguilar R, Gahl W, Bonifacino J . Altered trafficking of lysosomal proteins in Hermansky-Pudlak syndrome due to mutations in the beta 3A subunit of the AP-3 adaptor. Mol Cell. 1999; 3(1):11-21. DOI: 10.1016/s1097-2765(00)80170-7. View

Burgos P, Mardones G, Rojas A, daSilva L, Prabhu Y, Hurley J . Sorting of the Alzheimer's disease amyloid precursor protein mediated by the AP-4 complex. Dev Cell. 2010; 18(3):425-36. PMC: 2841041. DOI: 10.1016/j.devcel.2010.01.015. View

Harbour M, Breusegem S, Antrobus R, Freeman C, Reid E, Seaman M . The cargo-selective retromer complex is a recruiting hub for protein complexes that regulate endosomal tubule dynamics. J Cell Sci. 2010; 123(Pt 21):3703-17. PMC: 2964111. DOI: 10.1242/jcs.071472. View

Luzio J, Pryor P, Bright N . Lysosomes: fusion and function. Nat Rev Mol Cell Biol. 2007; 8(8):622-32. DOI: 10.1038/nrm2217. View

Slabicki M, Theis M, Krastev D, Samsonov S, Mundwiller E, Junqueira M . A genome-scale DNA repair RNAi screen identifies SPG48 as a novel gene associated with hereditary spastic paraplegia. PLoS Biol. 2010; 8(6):e1000408. PMC: 2893954. DOI: 10.1371/journal.pbio.1000408. View

Vojtek A, Hollenberg S . Ras-Raf interaction: two-hybrid analysis. Methods Enzymol. 1995; 255:331-42. DOI: 10.1016/s0076-6879(95)55036-4. View

Dokudovskaya S, Waharte F, Schlessinger A, Pieper U, Devos D, Cristea I . A conserved coatomer-related complex containing Sec13 and Seh1 dynamically associates with the vacuole in Saccharomyces cerevisiae. Mol Cell Proteomics. 2011; 10(6):M110.006478. PMC: 3108837. DOI: 10.1074/mcp.M110.006478. View

10.

Boehm M, Bonifacino J . Genetic analyses of adaptin function from yeast to mammals. Gene. 2002; 286(2):175-86. DOI: 10.1016/s0378-1119(02)00422-5. View

11.

Page L, Robinson M . Targeting signals and subunit interactions in coated vesicle adaptor complexes. J Cell Biol. 1995; 131(3):619-30. PMC: 2120623. DOI: 10.1083/jcb.131.3.619. View

12.

Schledzewski K, Brinkmann H, Mendel R . Phylogenetic analysis of components of the eukaryotic vesicle transport system reveals a common origin of adaptor protein complexes 1, 2, and 3 and the F subcomplex of the coatomer COPI. J Mol Evol. 1999; 48(6):770-8. DOI: 10.1007/pl00006521. View

13.

Fritz-Laylin L, Prochnik S, Ginger M, Dacks J, Carpenter M, Field M . The genome of Naegleria gruberi illuminates early eukaryotic versatility. Cell. 2010; 140(5):631-42. DOI: 10.1016/j.cell.2010.01.032. View

14.

Hirst J, Bright N, Rous B, Robinson M . Characterization of a fourth adaptor-related protein complex. Mol Biol Cell. 1999; 10(8):2787-802. PMC: 25515. DOI: 10.1091/mbc.10.8.2787. View

15.

Robinson M . Adaptable adaptors for coated vesicles. Trends Cell Biol. 2004; 14(4):167-74. DOI: 10.1016/j.tcb.2004.02.002. View

16.

Faulstich D, Auerbach S, Orci L, Ravazzola M, Wegchingel S, Lottspeich F . Architecture of coatomer: molecular characterization of delta-COP and protein interactions within the complex. J Cell Biol. 1996; 135(1):53-61. PMC: 2121028. DOI: 10.1083/jcb.135.1.53. View

17.

Sagona A, Nezis I, Pedersen N, Liestol K, Poulton J, Rusten T . PtdIns(3)P controls cytokinesis through KIF13A-mediated recruitment of FYVE-CENT to the midbody. Nat Cell Biol. 2010; 12(4):362-71. DOI: 10.1038/ncb2036. View

18.

Field M, Gabernet-Castello C, Dacks J . Reconstructing the evolution of the endocytic system: insights from genomics and molecular cell biology. Adv Exp Med Biol. 2007; 607:84-96. DOI: 10.1007/978-0-387-74021-8_7. View

19.

Hanein S, Martin E, Boukhris A, Byrne P, Goizet C, Hamri A . Identification of the SPG15 gene, encoding spastizin, as a frequent cause of complicated autosomal-recessive spastic paraplegia, including Kjellin syndrome. Am J Hum Genet. 2008; 82(4):992-1002. PMC: 2427184. DOI: 10.1016/j.ajhg.2008.03.004. View

20.

Blackstone C, OKane C, Reid E . Hereditary spastic paraplegias: membrane traffic and the motor pathway. Nat Rev Neurosci. 2010; 12(1):31-42. PMC: 5584382. DOI: 10.1038/nrn2946. View