Molecular correlates of syncytialization in muscle and placenta.

Syncytialization is one of the most fundamental processes in life. It is observed during development of muscle and osteoclast, and syncytiotrophoblast formation in placental villi. Syncytialization involves recognition, migration, adhesion and finally cell fusion between two interacting cells. It is an energy-dependent process which is essentially restricted to a small portion of interacting cellular membranes. Such regions of membranes may differ from other regions of cell surface in terms of physico-chemistry and expression of specific protein biomolecules resulting in restriction of this process to cells of specific competence. Despite the fact that membrane biologists have given significant quanta of efforts to understand the basic principle underlying this fundamental process of life, further large scale initiatives have to be undertaken to dissect the underlying molecular correlates central to this event.

Viral membrane fusion: is glycoprotein G of rhabdoviruses a representative of a new class of viral fusion proteins?

Enveloped viruses always gain entry into the cytoplasm by fusion of their lipid envelope with a cell membrane. Some enveloped viruses fuse directly with the host cell plasma membrane after virus binding to the cell receptor. Other enveloped viruses enter the cells by the endocytic pathway, and fusion depends on the acidification of the endosomal compartment. In both cases, virus-induced membrane fusion is triggered by conformational changes in viral envelope glycoproteins. Two different classes of viral fusion proteins have been described on the basis of their molecular architecture. Several structural data permitted the elucidation of the mechanisms of membrane fusion mediated by class I and class II fusion proteins. In this article, we review a number of results obtained by our laboratory and by others that suggest that the mechanisms involved in rhabdovirus fusion are different from those used by the two well-studied classes of viral glycoproteins. We focus our discussion on the electrostatic nature of virus binding and interaction with membranes, especially through phosphatidylserine, and on the reversibility of the conformational changes of the rhabdovirus glycoprotein involved in fusion. Taken together, these data suggest the existence of a third class of fusion proteins and support the idea that new insights should emerge from studies of membrane fusion mediated by the G protein of rhabdoviruses. In particular, the elucidation of the three-dimensional structure of the G protein or even of the fusion peptide at different pH's might provide valuable information for understanding the fusion mechanism of this new class of fusion proteins.