Molecular insights into the targeting of proteins to the inner nuclear membrane

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The proper functioning of our organs and tissues is intrinsically linked to the cells that compose them. Similarly, the smooth operation of these cells is in part dependent on the correct partitioning of proteins within the right cellular compartments. For instance, proteins involved in the regulation of our genes are targeted to the nucleus, where our chromosomes are found. This is typically achieved via pores in the nuclear envelope that specifically import proteins containing a unique postal code, i.e. a given sequence of amino acids. This process is relatively well understood for soluble proteins. For proteins that are integrated in the envelope of the nucleus, a novel targeting signal has only recently been found. However, the mechanism for that import remains is still enigmatic. Since all viruses are obligatory parasites that rely on cellular functions to multiply and much simpler organisms than us, they constitute excellent models to study cells. We have recently shown that the targeting to the nuclear envelope of a particular viral protein encoded by the herpes simplex virus type 1 genome does not follow the classical rules. Unlike any cellular proteins, this protein can also be found elsewhere in the cells and onto mature viruses. This protein gives us a very unique opportunity to probe nuclear targeting. In the long run, the present research program will examine whether the nuclear targeting machinery is universal, how it is regulated and whether viruses can modulate or perhaps even monopolize it. This research program should over the next decade or two elucidate this very complex biological machinery.