This study reveals a much more dynamic "before" picture, with structures that precondition the cell to respond to signals. The researchers say that their work clearly demonstrates how "resting" receptor movements are functionally relevant to the transmission of signals into the cell.
Grinstein, a senior scientist at Toronto's Hospital for Sick Children whose interests include understanding how macrophages work, approached Danuser for imaging and analysis expertise. Grinstein wanted to study CD36 at the single-molecule level in live cells and in real time under a microscope.
Using an automated particle-tracking algorithm she had developed to overcome the challenges of imaging such minute, complex interactions, Jaqaman analyzed these single-molecule movies to dissect the receptor behavior and its regulation.
The movies reveal three kinds of motion by the receptors, which are sensitive to strands of the cytoskeleton's actin meshwork adjacent to the cell surface. As receptors roam about, they bump into these strands, slowing, stopping or changing direction. Some wander freely about the surface of the cell. Others become temporarily stuck inside a pocket of the mesh, as if trapped in a cage. Finally, some of the receptors travel linear paths.
These paths follow elongated "corridors" alongside the cell's microtubules, another part of the cell's cytoskeleton, radiating in more-or-less straight lines from the nucleus.
How the corridors form remains a mystery. The researchers suspect that they emerge from interactions between microtubules and actin, which remove actin strands from the path of the receptors.
In these narrow corridors free of actin strands, receptors scurry to and fro with more freedom, regularly bumping into one another, forming clusters that stick together fleetingly and then drift apart.
The researches su
|Contact: David Cameron|
Harvard Medical School