Koumandou, V. L., Dacks, J. B., Coulson, R. M. & Field, M. C. Control systems for membrane fusion in the ancestral eukaryote; evolution of tethering complexes and SM proteins. BMC Evol. Biol. 7, 29

Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK. <>
BMC Evolutionary Biology (Impact Factor: 3.37). 02/2007; 7:29. DOI: 10.1186/1471-2148-7-29
Source: PubMed


In membrane trafficking, the mechanisms ensuring vesicle fusion specificity remain to be fully elucidated. Early models proposed that specificity was encoded entirely by SNARE proteins; more recent models include contributions from Rab proteins, Syntaxin-binding (SM) proteins and tethering factors. Most information on membrane trafficking derives from an evolutionarily narrow sampling of model organisms. However, considering factors from a wider diversity of eukaryotes can provide both functional information on core systems and insight into the evolutionary history of the trafficking machinery. For example, the major Qa/syntaxin SNARE families are present in most eukaryotic genomes and likely each evolved via gene duplication from a single ancestral syntaxin before the existing eukaryotic groups diversified. This pattern is also likely for Rabs and various other components of the membrane trafficking machinery.
We performed comparative genomic and phylogenetic analyses, when relevant, on the SM proteins and components of the tethering complexes, both thought to contribute to vesicle fusion specificity. Despite evidence suggestive of secondary losses amongst many lineages, the tethering complexes are well represented across the eukaryotes, suggesting an origin predating the radiation of eukaryotic lineages. Further, whilst we detect distant sequence relations between GARP, COG, exocyst and DSL1 components, these similarities most likely reflect convergent evolution of similar secondary structural elements. No similarity is found between the TRAPP and HOPS complexes and the other tethering factors. Overall, our data favour independent origins for the various tethering complexes. The taxa examined possess at least one homologue of each of the four SM protein families; since the four monophyletic families each encompass a wide diversity of eukaryotes, the SM protein families very likely evolved before the last common eukaryotic ancestor (LCEA).
These data further support a highly complex LCEA and indicate that the basic architecture of the trafficking system is remarkably conserved and ancient, with the SM proteins and tethering factors having originated very early in eukaryotic evolution. However, the independent origin of the tethering complexes suggests a novel pattern for increasing complexity in the membrane trafficking system, in addition to the pattern of paralogous machinery elaboration seen thus far.

Download full-text


Available from: Mark Field
    • "The two known vCLAMPs proteins, Vps39 and Rab7, are involved in many membrane trafficking processes464748. Of these two, Rab7 is present in virtually every eukaryote, while Vps39 is present in most eukaryotes but absent from alveolates [95,96]. It is currently unclear whether or not vCLAMPs form in organisms other than S. cerevisiae. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The ER-mitochondria organizing network (ERMIONE) in Saccharomyces cerevisiae is involved in maintaining mitochondrial morphology and lipid homeostasis. ERMES and MICOS are two scaffolding complexes of ERMIONE that contribute to these processes. ERMES is ancient but has been lost in several lineages including animals, plants, and SAR (stramenopiles, alveolates and rhizaria). On the other hand, MICOS is ancient and has remained present in all organisms bearing mitochondrial cristae. The ERMIONE precursor evolved in the α-proteobacterial ancestor of mitochondria which had the central subunit of MICOS, Mic60. The subsequent evolution of ERMIONE and its interactors in eukaryotes reflects the integrative co-evolution of mitochondria and their hosts and the adaptive paths that some lineages have followed in their specialization to certain environments. By approaching the ERMIONE from a perspective of comparative evolutionary cell biology, we hope to shed light on not only its evolutionary history, but also how ERMIONE components may function in organisms other than S. cerevisiae.
    No preview · Article · Jan 2016 · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
    • "For human Vps53 and Vps54 it was found that they can also bind the SNAREs Syntaxin6, Syntaxin16 and VAMP4 [148]. The single subunits contain alternating short coiled-coils connecting a-helical stretches [96,142,143,146,149–151] with homology to other CATCHR members as Dsl, COG or exocyst [96] [97], and their N-terminal regions are responsible for complex assembly "
    [Show abstract] [Hide abstract]
    ABSTRACT: The HOPS multisubunit tethering factor (MTC) is a macromolecular protein complex composed of six different subunits. It is one of the key components in the perception and subsequent fusion of multivesicular bodies and vacuoles. Electron microscopy studies indicate structural flexibility of the purified HOPS complex. Inducing higher rigidity into HOPS by biochemically modifying the complex declines the potential to mediate SNARE-driven membrane fusion. Thus, we propose that integral flexibility seems to be not only a feature, but of essential need for the function of HOPS. This review focuses on the general features of membrane tethering and fusion. For this purpose, we compare the structure and mode of action of different tethering factors to highlight their common central features and mechanisms. Copyright © 2015. Published by Elsevier B.V.
    No preview · Article · Jun 2015 · FEBS letters
  • Source
    • "As an essential protein complex in yeast, it is required for the fusion of Golgi-derived vesicles with the ER. Two of the three subunits have homologs in humans that are involved in retrograde trafficking pathways between the Golgi and ER (48). Structural studies of the yeast Dsl1 complex indicate that Sec39 and Tip20 subunits are bridged by Dsl1 through interactions of the CATCHR domain of Dsl1 with that of Tip20 to assemble a 20 nm structure (68). "
    [Show abstract] [Hide abstract]
    ABSTRACT: CAPS (Calcium-dependent Activator Protein for Secretion, aka CADPS) and Munc13 (Mammalian Unc-13) proteins function to prime vesicles for Ca(2+)-triggered exocytosis in neurons and neuroendocrine cells. CAPS and Munc13 proteins contain conserved C-terminal domains that promote the assembly of SNARE complexes for vesicle priming. Similarities of the C-terminal domains of CAPS/Munc13 proteins with Complex Associated with Tethering Containing Helical Rods domains in multi-subunit tethering complexes (MTCs) have been reported. MTCs coordinate multiple interactions for SNARE complex assembly at constitutive membrane fusion steps. We review aspects of these diverse tethering and priming factors to identify common operating principles.
    Full-text · Article · Dec 2013 · Frontiers in Endocrinology
Show more

Similar Publications