The ubiquitous and ancient ER membrane protein complex (EMC): tether or not?

Abstract

The recently discovered endoplasmic reticulum (ER) membrane protein complex (EMC) has been implicated in ER-associated degradation (ERAD), lipid transport and tethering between the ER and mitochondrial outer membranes, and assembly of multipass ER-membrane proteins. The EMC has been studied in both animals and fungi but its presence outside the Opisthokont clade (animals + fungi + related protists) has not been demonstrated. Here, using homology-searching algorithms, I show that the EMC is truly an ancient and conserved protein complex, present in every major eukaryotic lineage. Very few organisms have completely lost the EMC, and most, even over 2 billion years of eukaryote evolution, have retained a majority of the complex members. I identify Sop4 and YDR056C in Saccharomyces cerevisiae as Emc7 and Emc10, respectively, subunits previously thought to be specific to animals. This study demonstrates that the EMC was present in the last eukaryote common ancestor (LECA) and is an extremely important component of eukaryotic cells even though its primary function remains elusive.

Keywords: ER membrane protein complex (EMC); ER-mitochondria contact sites; ERMES; Evolutionary cell biology; Membrane contact sites (MCS).

Figure 1.. Coulson plot showing distribution of EMC components across eukaryotes.

Coloured pies indicate presence of a particular subunit. Plot was generated using the Coulson plot generator ( Field et al., 2013). Asterisks indicate presence of orthologue in a different member of the genus but absent in the indicated species (see Table S1). Abbreviations: Vertebrates: Hsap, Homo sapiens; Mdom, Monodelphis domesticus; Drer, Danio rerio; Xtro, Xenopus tropicalis; Ggal, Gallus gallus; Mmus, Mus musculus; Invertebrates: Cele, Caenorhabditis elegans; Dmel, Drosophila melanogaster; Bflo, Branchiostoma floridae; Nvec, Nematostella vectensis; Tadh, Trichoplax adhaerens; Unicellular Holozoa: Mbre, Monosiga brevicollis; Cowc, Capsaspora owczarzaki; Sarc, Sphaeroforma arctica; Sros, Salpingoeca rosetta; Fungi: Spom, Schizosaccharomyces pombe; Scer, Saccharomyces cerevisiae; Ncra, Neurospora crassa; Cneo, Cryptococcus neoformans; Umay, Ustilago maydis; Bden, Batrachochytrium dendrobatidis; Ncer, Nosema ceranae; Ecun, Encephalitozoon cuniculi; Pir, Piromyces sp.; Spun, Spizellomyces punctatus; Rirr, Rhizophagus irregularis; Crev, Coemansia reversa; Ccor, Conidiobolus coronatus; Cang, Catenaria anguillulae; Rall, Rozella allomyces; Apusozoa: Ttra, Thecamonas trahens; Fonticulids: Fonticula alba; Amoebozoa: Acas, Acanthamoeba castellanii; Ddis, Dictyostelium discoideum; Ehis, Entamoeba histolytica; Ppal, Polysphondylium pallidum; Excavata: Ngru, Naegleria gruberi; Gint, Giardia intesinalis; Tvag, Trichomonas vaginalis; Bsal, Bodo saltans; Lmaj, Leishmania major; Tbru, Trypanosoma brucei; Stramenopiles: Bhom, Blastocystis hominis; Alim, Aurantiochytrium limacinum; Aana, Aureococcus anophagefferens; Tpse, Thalassiosira pseudonana; Ptri, Phaeodactylum tricornutum; Psoj, Phytophthora sojae; Esil, Ectocarpus siliculosus; Ngad, Nannochloropsis gaditana; Alveolates: Ptet, Paramecium tetraurelia; Tthe, Tetrahymena thermophila; Otri, Oxytricha trifallax; Tpar, Theileria parva; Smin, Symbiodinium minutum; Tgon, Toxoplasma gondii; Cpar, Cryptosporidium parvum; Pfal, Plasmodium falciparum; Rhizaria: Bnat, Bigelowiella natans; Rfil, Reticulomyxa filosa; Archaeplastida: Crei, Chlamydomonas reinhardtii; Cmer, Cyanidioschyzon merolae; Cyp, Cyanophora paradoxa; Atha, Arabidopsis thaliana; Ppat, Physcomitrella patens; Otau, Ostreococcus tauri; Gsul, Galdieria sulphuraria; Mpus, Micromonas pusilla; Ccri, Chondrus crispus; CCTH: Ehux, Emiliania huxleyi; Gthe, Guillardia theta.

Figure 2.. Evolutionary history of the EMC.

EMC 1-8 and 10 evolved prior to the divergence of the major eukaryote lineages. Green and red dashes represent gains and losses of EMC components, respectively. Coloured pies are schematic representations of which EMC components were present at different points over the course of evolution.

Supplementary Figure S1.. Phylogenetic analysis of opisthokont Emc8/9 proteins.

Proteins were aligned using MUSCLE ( Edgar, 2004) and manually adjusted as needed using Mesquite ( http://mesquiteproject.org). Phylogenetic tree reconstructions were carried out using MrBayes v3.2.2 ( Ronquist et al., 2003) for Bayesian analysis. Maximum likelihood bootstrap values were obtained using RaxML ( Stamatakis, 2006) with 100 pseudoreplicates using the LG model ( Le & Gascuel, 2008). Support values: MrBayes/RAxML. Only support values >0.90/50 are shown.