The Autocrine Mitogenic Loop of the Ciliate<i>Euplotes raikovi</i>: The Pheromone Membrane-bound Forms Are the Cell Binding Sites and Potential Signaling Receptors of Soluble Pheromones

Ortenzi, Claudio; Alimenti, Claudio; Vallesi, Adriana; Pretoro, Barbara Di; Terza, Antonietta La; Luporini, Pierangelo

doi:10.1091/mbc.11.4.1445

Cited by 43 publications

(36 citation statements)

References 48 publications

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“…Results from studies on E. raikovi (24) suggest that the pheromone receptors are membrane-bound pheromone isoforms, characterized in each cell type by an extracellular domain that is a structural counterpart to the secreted pheromone capable of selective, competitive binding to multiple closely homologous pheromone molecules (25). Mutual binding reactions between En-6 and En-A1 pheromone preparations were analyzed with Surface Plasmon Resonance experiments, by linking one preparation to a sensor chip to act as a ligand and injecting the second preparation into the flow chamber of the experimental apparatus to act as the analyte (Fig.…”

Section: Resultsmentioning

confidence: 99%

Antarctic and Arctic populations of the ciliate Euplotes nobilii show common pheromone-mediated cell-cell signaling and cross-mating

Giuseppe

Erra

Dini

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Wild-type strains of the protozoan ciliate Euplotes collected from different locations on the coasts of Antarctica, Tierra del Fuego and the Arctic were taxonomically identified as the morpho-species Euplotes nobilii, based on morphometric and phylogenetic analyses. Subsequent studies of their sexual interactions revealed that mating combinations of Antarctic and Arctic strains form stable pairs of conjugant cells. These conjugant pairs were isolated and shown to complete mutual gene exchange and cross-fertilization. The biological significance of this finding was further substantiated by demonstrating that close homology exists among the threedimensional structures determined by NMR of the water-borne signaling pheromones that are constitutively secreted into the extracellular space by these interbreeding strains, in which these molecules trigger the switch between the growth stage and the sexual stage of the life cycle. The fact that Antarctic and Arctic E. nobilii populations share the same gene pool and belong to the same biological species provides new support to the biogeographic model of global distribution of eukaryotic microorganisms, which had so far been based exclusively on studies of morphological and phylogenetic taxonomy.ciliate mating types and sexual interactions | microbial ecology | NMR structures | polar biology | signaling by water-borne pheromones

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Section: Resultsmentioning

confidence: 99%

Antarctic and Arctic populations of the ciliate Euplotes nobilii show common pheromone-mediated cell-cell signaling and cross-mating

Giuseppe

Erra

Dini

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…This p15 internalization appears to be specifically required to activate the transduction pathway that controls the cell growth response, and the presence in the p15 cytoplasmic domain of two potential phosphorylation sites for protein kinases A and C, identified by the R/KXXS sequence (24), makes it likely that it involves an Er-1-induced p15 phosphorylation. Support for the cause-effect relationship that links Er-1-induced p15 internalization to the cell growth response was provided by the observation that cells no longer internalize p15 bound to another (nonself) pheromone such as Er-2, which was used in this study as a competitive analogue of Er-1.…”

Section: Discussionmentioning

confidence: 99%

“…When its translation product is processed, the entire C-terminal prepropheromone is retained as an extracellular peptide anchored to the cell surface through the "pre" transmembrane segment, and the N terminus is intracellular (13,20). It is this membrane-bound pheromone isoform that cells utilize as a specific pheromone receptor (24).…”

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“…For type I cells secreting the pheromone Er-1, it was previously shown that the pheromone receptor, represented by a 15-kDa protein of 130 amino acids, originally designated "Er1mem" and hereafter called "p15," can effectively utilize its extracellular domain for both autocrine and paracrine pheromone binding and its intracellular domain to trigger a mitogenic transduction pathway (24). In the 55-amino-acid sequence of this intracellular domain, there are potential sites for the phosphorylation of protein kinases as well as for receptor associations with GTP binding proteins.…”

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Autocrine, Mitogenic Pheromone Receptor Loop of the Ciliate Euplotes raikovi : Pheromone-Induced Receptor Internalization

et al. 2005

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The ciliate Euplotes raikovi produces a family of diffusible signal proteins (pheromones) that function as prototypic growth factors. They may either promote cell growth, by binding to pheromone receptors synthesized by the same cells from which they are secreted (autocrine activity), or induce a temporary cell shift from the growth stage to a mating (sexual) one by binding to pheromone receptors of other, conspecific cells (paracrine activity). In cells constitutively secreting the pheromone Er-1, it was first observed that the expression of the Er-1 receptor "p15," a type II membrane protein of 130 amino acids, is quantitatively correlated with the extracellular concentration of secreted pheromone. p15 expression on the cell surface rapidly and markedly increased after the removal of secreted Er-1 and gradually decreased in parallel with new Er-1 secretion. It was then shown that p15 is internalized through endocytic vesicles following Er-1 binding and that the internalization of p15/Er-1 complexes is specifically blocked by the paracrine p15 binding of Er-2, a pheromone structurally homologous to, and thus capable of fully antagonizing, Er-1. Based on previous findings that the p15 pheromone-binding site is structurally equivalent to Er-1 and that Er-1 molecules polymerize in crystals following a pattern of cooperative interaction, it was proposed that p15/Er-1 complexes are internalized as a consequence of their unique property (not shared by p15/Er-2 complexes) of undergoing clustering.In association with the evolution of systems of multiple cell (mating) types controlling self/nonself recognition phenomena, species of Euplotes synthesize families of structurally homologous soluble proteins that confer on cells a chemical specificity, with each protein representing a diffusible chemical signal (pheromone) that distinguishes one cell type from all the others (17). Euplotes raikovi is the species with which these pheromones, designated Er-1, Er-2, and so forth, have been better characterized with regard to their structure and function. Pheromones are small molecules of 38 to 50 amino acids with a common architecture based on a bundle of three ␣-helices fastened together by three conserved disulfide bonds (16,26,35). They have at least two activities each, acting as both prototypic autocrine growth factors and paracrine mating (sexual) signals (31). Upon binding their own pheromones, which cells constitutively secrete into the extracellular environment throughout the cell cycle, cells grow vegetatively and divide mitotically. When cells bind a nonself pheromone from another cell type, they temporarily arrest their growth and develop competence for uniting in mating pairs (23). We refer to the response to self pheromones as an autocrine response and the response to nonself pheromones as a paracrine response.The field addressing the issue of how cells can discriminate between autocrine and paracrine pheromone binding and accordingly mount a growth or mating response was advanced by the identification of the pher...

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“…In the ciliate Euplotes raikovi, mating pheromones (euplomones) are synthesized constitutively throughout the entire clonal life cycle and in growing cells (Miceli et al, 1989;Luporini et al, 1992;Miceli et al, 1992;Vallesi et al, 1995;Luporini et al, 1995;Ortenzi et al, 2000). The gene encoding each pheromone generates at least two distinct molecules by alternative splicing, one of which is the soluble pheromone and the other a membrane-bound pheromone isoform.…”

Section: Discussionmentioning

confidence: 99%

Developmentally and environmentally regulated expression of gamone 1: the trigger molecule for sexual reproduction inBlepharisma japonicum

Sugiura

Kawahara

Iio

et al. 2005

Journal of Cell Science

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Sexual reproduction (conjugation) in protozoan ciliates is induced by specific cell-cell interactions between cells of complementary mating types. The ancestral ciliate Blepharisma japonicum has two mating types, I and II. The substances that act as signaling molecules in this extracellular interaction for conjugation are called gamones. The glycoprotein gamone 1, produced by mating type I cells, is a key factor that triggers this interaction. We have previously isolated gamone 1 and determined its complete amino acid sequence. To elucidate the mechanism of initiation of conjugation in ciliates, we investigated the transcription of the gamone 1 gene and found that it is controlled by various internal and external factors. The gamone 1 gene transcript appeared specifically when sexually mature mating type I cells were starved. It was not detected in immature cells, mating type II cells or proliferating cells. The level of transcription was markedly increased in type I cells when they were stimulated with gamone 2, which is secreted by type II cells. This is the first report that the transcription of gamone genes in ciliates is strictly regulated by developmental and environmental factors. This study suggests that the onset of transcription of gamone 1 is linked to the switching mechanism that converts mitotically proliferating cells to differentiated preconjugants, the mechanism of differentiation from immature to mature cells in clonal development, and the mechanism that ensures mating type-specific gene silencing.

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The Autocrine Mitogenic Loop of the CiliateEuplotes raikovi: The Pheromone Membrane-bound Forms Are the Cell Binding Sites and Potential Signaling Receptors of Soluble Pheromones

Cited by 43 publications

References 48 publications

Antarctic and Arctic populations of the ciliate Euplotes nobilii show common pheromone-mediated cell-cell signaling and cross-mating

Antarctic and Arctic populations of the ciliate Euplotes nobilii show common pheromone-mediated cell-cell signaling and cross-mating

Autocrine, Mitogenic Pheromone Receptor Loop of the Ciliate Euplotes raikovi : Pheromone-Induced Receptor Internalization

Developmentally and environmentally regulated expression of gamone 1: the trigger molecule for sexual reproduction inBlepharisma japonicum

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