Parijat –

 Some studies have reported that phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P(2)] operates as a link between cholesterol and actin filaments. As you have noted, induction of  actin polymerization at the cell periphery owing to cholesterol depletion has also been reported. 

Dear Parijat,

This is an interesting question. I have been thinking similar things myself as cholesterol levels or trafficking (in a sense) is tightly linked to the endomembrane system (Pi(3)Ps, Pi(4,5)Ps that make up endosomes, lysosomes, endo-lysosomes...etc.), which itself is tightly linked to the cytoskeleton.

I do believe that both are in a loop together, linking cell periphery to intra-cellular sensing. Both would be needed to generate an output of cellular activity that covers both intra-cellular and extra-cellular environments.

There are many cell based diseases that are the result of loss of cholesterol or even loss of cholesterol trafficking. The deeper mechanism involves multiple factors that can be summarised into: correct trafficking of lysosomes and well regulated tubulin and actin cytoskeletons. When both of these factors are mis-regulated then the resulting lysosomal build-up leads to a defect in cholesterol.

There has been a recent publication in Drosophila that highlights the link between trafficking and the cytoskeleton: Evans, et al., 2013, Cell Death and Differentiation, 20(5): pp. 709-720. This paper comments on overall cell disruption from the cytoskeleton toward the trafficking systems, which is one of the first papers out there commenting so.

Outside of that I would also suggest you look at papers covering actin nucleation from the endosomal surface complex WASH. It certainly is an interesting read, and you will start to see the connections between the dots as such!

I really hope this helps, and good luck!

Best regards,

Chris

Dear Parijat,

From the molecular biological or cell biological experiments, there seems to be reported results suggesting the relationship between cholesterol regulation and actin cytoskeletons.

However, I would like to mention that, still existence of such systems has not been confirmed, in the biochemical and biophysical methods.

Even if it actually works in cells, the mechanism has not been revealed.

The regulatory system, such as PIP2 is involved, would be expected.

However, whether really there is interactions between the factors expected involvement, membrane regulations including cholesterol and actin cytoskeletons, it is the progress of study yet.