The standard way to enter into the nucleus is through the nuclear pore, and it is fairly tightly regulated. The nuclear pore "works much like a gated ion channel," Ray Gavin, a professor of biology, told BioWorld Today. "A protein must interact with some of the guardian proteins" lining the nuclear pore to gain entry, via specific peptide sequences known as nuclear localization sequences.

But in the Aug. 10, 2007 issue of Cell Motility and the Cytoskeleton, senior author Gavin and first author Roland Hosein, both at Brooklyn College of the City University of New York, described what may be a way to gate-crash. In the unicellular organism tetrahymena, the researchers observed both phagosomes depositing their contents directly into the nucleus.

Phagosomes are a somewhat limited phenomenon in higher organisms, though they are a standard way for immune system macrophages to deal with infectious agents. But the scientists observed a similar phenomenon with endosomes. Given that endocytosis occurs in most cells, Gavin said that the direct entry of material into the nucleus "could be far more extensive than we ever imagined."

The way phagosomes appear to achieve that feat is by teaming up with what's known as "unconventional" myosin, which does not form filaments. Myosin probably is best known for its starring role in muscle contraction.

The unconventional myosin described by Hosein and Gavin also forms complexes with actin, and those actin-myosin complexes are necessary for the phagosomes to move through the cell, though Gavin said that it is unclear whether the actin-myosin or some other as yet unidentified protein acts as the molecular motor that propels them.

In the experiments described in their paper, Hosein and Gavin tracked phagosomes carrying extracellular material into the cell nuclei by introducing fluorescent latex beads into the extracellular medium. Most phagosomes moved to the posterior region of the cell, fusing with other endosomes and lysosomes on the way, and ultimately were recycled back out of the cell.

But some phagosomes took the road less traveled: They went to the nucleus and deposited their contents into it. Gavin said the direct entry amounts to eliminating the middleman. "One less step is needed for extracellular material to get into the nucleus, and so it is far easier than previously thought for this material to get into the nucleus."

For now, the discoveries are firmly in the realm of basic research. "We don't have any good clues at this point of what targets some phagosomes to the nucleus," Gavin said - or even whether there is a targeting system. The process theoretically could be random, though given the importance of controlling what goes into the nucleus, that seems unlikely.

Once it's clear what makes certain phagosomes go to the nucleus, however, the findings "could certainly have drug delivery implications," Gavin said. "Biologists may now study the kinds of external molecules that can gain entry to the nucleus through these newly defined pathways and how these materials influence the nucleic material and its processes."