IMB team first to ID endocytosis mechanism

Electron microscopists at the University of Queensland's Institute for Molecular Bioscience have spotted the first, sub-microscopic components of the molecular machinery of endocytosis -- the process by which living cells take up nutrients and particles.

Prof Rob Parton's research group has identified structures 100,000th of a millimetre in diameter that mediate the earliest steps of endocytosis.

A fuller understanding the process could allow chemists to exploit the cell's own import machinery to deliver drugs into cells. Some viruses hijack the endocytosis pathway to invade cells, so an understanding of the process could lead to the development of new antiviral drugs, Parton said.

The IMB team describes its discovery in a paper in this month's issue of The Journal of Cell Biology.

"This new pathway was long suspected, however our work was the first to conclusively prove its existence and to identify the cellular structures involved," Parton said.

In addition to opening new avenues for antiviral drugs, or for drug delivery and gene therapy, the IMB researchers believe studies of the molecular machinery of endocytosis will provide new insights into the evolution of complex organisms. Parton said the next step was to identify the proteins and genes involved in endocytosis.

Cells require a continuous, regulated flux of nutrients and other chemicals to survive. The cell membrane invaginates, trapping the particles within a bubble of membrane; a sphincter then pinches the neck of the bubble shut, sealing the hole in the membrane and leaving the contents of the vesicle inside the cell.

Parton said the continuous process consumes the equivalent of the entire area of the cell membrane every 30 minutes -- the lipid membrane is constantly recycled and rebuilt to balance the loss.

"We've been interested in endocytosis for many years, and the main pathway is pretty well characterised," he said. "But there has always been indirect evidence that there are multiple pathways into cells, really fundamental processes common to all mammalian cells, and even organisms as simple as yeasts.

"We decided to use electron microscopy to find out what we could about alternate pathways into the cell that people had speculated about, but never seen. It has been a major collaboration between researchers in Australia, India and the US.

"We've been able to identify the first carriers in an alternate pathway."

Parton said the new evidence suggests that, in addition to the import role performed by protein receptors anchored in the cell membrane, there are distinct patches of specialised lipids within the membrane that also act as receptors for particular classes of nutrients and particles.

Viruses with lipophilic proteins, and bacteria with lipopolysaccharide cell walls may exploit these patches to infect cells.

"We know a lot about the machinery of the other pathway, and how it is regulated, but almost nothing about this alternative pathway," Parton said.

"We need to know how the lipid patches work in their selective manner -- they appear to be particularly sensitive to cholesterol, so if you change cholesterol levels in the body, it may change the way cells absorb nutrients and particles."

Omega-3 polyunsaturated fatty acids also appear to change the properties of the lipid patches, hinting that the health benefits of omega-3 oils may stem from changes in the way cells take up nutrients.