Genetic basis of cell–cell fusion mechanisms

Abstract

Cell-cell fusion in sexually reproducing organisms is a mechanism to merge gamete genomes, and in multicellular organisms, it is a strategy to sculpt organs such as muscles, bones, and placenta. Moreover, this mechanism has been implicated in pathological conditions such as infection and cancer. Study of genetic model organisms has uncovered a unifying principle: cell fusion is a genetically programmed process. This process can be divided in three stages: (i) competence: cell induction and differentiation, (ii) commitment: cell determination, migration and adhesion, and (iii) cell fusion: membrane merging and cytoplasmic mixing. Recent work has led to the discovery of fusogens, cell fusion proteins that are necessary and sufficient to fuse cell membranes. Two unrelated families of fusogens have been discovered, one in mouse placenta and one in Caenorhabditis elegans (Syncytins and F proteins, respectively). Current research aims to identify new fusogens and determine the mechanisms by which fusogens merge membranes.

Cell behaviors and dynamics during angiogenesis

“…While cell-cell fusion is a prominent process during development and occurs during the fusion of gametes, the generation of multinucleate muscle fibers and during placenta formation (Aguilar et al, 2013;Demonbreun et al, 2015;Kim et al, 2015;Pérez-Vargas et al, 2014;Podbilewicz, 2014), cell self-fusion is a much rarer phenomenon, but has been well described in C. elegans (Rasmussen et al, 2008). Since, in these particular cases, cells fuse with themselves (as illustrated in Fig.…”

Spatiotemporal regulation of cell fusion by JNK and JAK/STAT signaling during Drosophila wound healing

“…Cell fusion thus needs to be under tight control to prevent spontaneous and, once initiated, excessive fusion. Cell fusion occurs widely in developmental and disease processes, including fertilization, muscle formation, bone resorption, infection and tumorigenesis (Chen and Olson, 2005;Shinn-Thomas and Mohler, 2011;Aguilar et al, 2013). However, no general picture for cell fusion has emerged to date and the mechanisms by which cell fusion is initiated, and at the same time confined to specific cells or tissue areas, has not been well studied.…”

Spatial focalization of pheromone/MAPK signaling triggers commitment to cell–cell fusion

“…Third, a fusion machinery is assembled at the cell-cell contact site for membrane merging. This machinery may be composed of two main parts: a specific actin structure that promotes membrane juxtaposition (Abmayr and Pavlath 2012) and fusogenic proteins that drive membrane fusion (Aguilar et al 2013). In walled cells, such as fungal or plant cells, the process is further complicated because the cell wall first needs to be locally degraded while preserving cell integrity.…”