AFF-1, a FOS-1-Regulated Fusogen, Mediates Fusion of the Anchor Cell in C. elegans

Sapir, Amir; Choi, Jaebok; Leikina, Evgenia; Avinoam, Ori; Valansi, Clari; Chernomordik, Leonid V.; Newman, Anna P.; Podbilewicz, Benjamin

doi:10.1016/j.devcel.2007.03.003

Cited by 131 publications

(192 citation statements)

References 31 publications

Supporting

Mentioning

186

Contrasting

Order By: Relevance

“…Doberstein et al (1997) postulated that the vesicles of the prefusion complex dissolve to form electron-dense plaques. Alternatively, these vesicles may play a role in transporting fusion-relevant molecules to the site of fusion, and such molecules might be analogous to the fusogenes Eff1 and Aff1 identified in epithelial fusion in C. elegans (Mohler et al, 2002;Podbilewicz et al, 2006;Sapir et al, 2007). Although such fusogenes have so far not been identified in Drosophila, one could hypothesize that such proteins might trigger membrane vesiculation and subsequent breakdown during myoblast fusion.…”

Section: The Furmas Model For Myoblast Fusion: Key Molecular Playersmentioning

confidence: 99%

FuRMAS: triggering myoblast fusion in Drosophila

Önel

Renkawitz‐Pohl

2009

Developmental Dynamics

View full text Add to dashboard Cite

In Drosophila, as in mammals, myoblast fusion is fundamental for development. This fusion process has two distinct phases that share common ultrastructural features and at least some molecular players between Drosophila and vertebrates. Here, we integrate the latest data on the key molecular players and ultrastructural features found during myoblast fusion into a new working model to explain this fundamental cellular process. At cell-cell contact sites, a protein complex (

show abstract

Section: The Furmas Model For Myoblast Fusion: Key Molecular Playersmentioning

confidence: 99%

FuRMAS: triggering myoblast fusion in Drosophila

Önel

Renkawitz‐Pohl

2009

Developmental Dynamics

View full text Add to dashboard Cite

show abstract

“…Formation of syncytia in C. elegans depends on a single protein (EFF-1 or AFF-1) (Mohler et al 2002;del Campo et al 2005;Sapir et al 2007), but the fusogen must be present on both of the fusing membranes (Podbilewicz et al 2006). And myoblast fusion requires a mix of conserved and species-limited proteins for prefusion attachment, signaling, and cytoskeletal rearrangements (Chen and Olson 2005).…”

Section: Mechanisms Of Gamete Fusionmentioning

confidence: 99%

The conserved plant sterility gene HAP2 functions after attachment of fusogenic membranes in Chlamydomonas and Plasmodium gametes

Liu¹,

Tewari²,

Ning³

et al. 2008

Genes Dev.

305

386

View full text Add to dashboard Cite

The cellular and molecular mechanisms that underlie species-specific membrane fusion between male and female gametes remain largely unknown. Here, by use of gene discovery methods in the green alga Chlamydomonas, gene disruption in the rodent malaria parasite Plasmodium berghei, and distinctive features of fertilization in both organisms, we report discovery of a mechanism that accounts for a conserved protein required for gamete fusion. A screen for fusion mutants in Chlamydomonas identified a homolog of HAP2, an Arabidopsis sterility gene. Moreover, HAP2 disruption in Plasmodium blocked fertilization and thereby mosquito transmission of malaria. HAP2 localizes at the fusion site of Chlamydomonas minus gametes, yet Chlamydomonas minus and Plasmodium hap2 male gametes retain the ability, using other, species-limited proteins, to form tight prefusion membrane attachments with their respective gamete partners. Membrane dye experiments show that HAP2 is essential for membrane merger. Thus, in two distantly related eukaryotes, species-limited proteins govern access to a conserved protein essential for membrane fusion.[Keywords: Gamete fusion; cell-cell fusion; malaria; HAP2; Chlamydomonas, Plasmodium] Supplemental material is available at http://www.genesdev.org. Received January 28, 2008; revised version accepted February 22, 2008. Fusion of gametes of opposite sex (or mating type) to form a zygote is the defining moment in the life of a eukaryote. In the first phase of gamete interactions, cell adhesion molecules displayed on the surfaces of the gametes bring the two cells together. In animals, the sperm plasma membrane binds to the extracellular matrix of the egg (the zona pellucida in mammals and the jelly coat in many invertebrates). The interacting gametes use this first-phase adhesion step not only to bind to each other, but also to initiate a signal transduction cascade that activates the sperm and exposes new, fusogenic regions of the sperm plasma membrane. In the second phase of fertilization, the membrane fusion reaction, the plasma membranes of the two gametes come into intimate contact and then fuse, bringing about cytoplasmic continuity (Primakoff and Myles 2002;Rubinstein et al. 2006). Although these two steps-prefusion attachment of the plasma membranes of gametes and merger of their lipid bilayers-have been experimentally separated using in vitro bioassays, gene disruption studies to date have failed to distinguish the two, and no genes have been identified whose disruption allows prefusion attachment and disallows membrane merger. In mice, several proteins involved in gamete membrane interactions have been described, including ADAMS family members and CRISP proteins on sperm and integrins and tetraspanin family members CD9 and CD81 on eggs (for review, see Ellerman et al. 2006;Inoue et al. 2007;Primakoff and Myles 2007). Izumo, an immunoglobulin superfamily sperm protein that appears to be limited to mammals, is gamete-specific and shown by gene disruption to be essential at a late step in ferti...

show abstract

“…Disulfide bonds within the human immunodeficiency virus fusion protein must be rearranged by protein disulfide isomerase isoforms present on the cell surface to permit a conformational shift required for membrane merger (24 -26). Disulfide bonds are also likely to be critical for the function of non-viral fusogens because extracellular cysteine-rich domains are present in proteins required for both developmental (EFF-1 and AFF-1) and germ line (SPE-38) fusions in C. elegans (20,27).…”

Section: Discussionmentioning

confidence: 99%

Prm1 Functions as a Disulfide-linked Complex in Yeast Mating

Olmo

Grote

2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

Prm1 is a pheromone-induced membrane glycoprotein that promotes plasma membrane fusion in yeast mating pairs. HAPrm1 migrates at twice its expected molecular weight on nonreducing SDS-PAGE gels and coprecipitates with Prm1-TAP, indicating that Prm1 is a disulfide-linked homodimer. The N terminus of a plasma membrane-localized GFP-Prm1 endocytic mutant projects into the cytoplasm, where it is protected from low pH quenching in live cells and from external protease in spheroplasts. In a revised topological map, Prm1 has four transmembrane domains and two large extracellular loops. Mutation of all four cysteines in the extracellular loops blocked disulfide bond formation and destabilized the Prm1 homodimer without preventing Prm1 transport to contact sites in mating pairs. Cys 120 in loop 1 and Cys 545 in loop 2 form disulfide cross-links in the Prm1 homodimer and are required for fusion activity. Cys 120 lies between a hydrophobic segment formerly thought to be a transmembrane domain and an amphipathic helix. An interaction between either of these regions and the opposing membrane could promote fusion.

show abstract

AFF-1, a FOS-1-Regulated Fusogen, Mediates Fusion of the Anchor Cell in C. elegans

Cited by 131 publications

References 31 publications

FuRMAS: triggering myoblast fusion in Drosophila

FuRMAS: triggering myoblast fusion in Drosophila

The conserved plant sterility gene HAP2 functions after attachment of fusogenic membranes in Chlamydomonas and Plasmodium gametes

Prm1 Functions as a Disulfide-linked Complex in Yeast Mating

Contact Info

Product

Resources

About