intermediate filaments - (Jan/09/2008 )

dear all

i'm looking for a drug to perturb intermediate filaments networks in order to induce their depolymerization!
can you help me?

all regards!

Hi,

Thats going to be hard to find, intermediate filaments spontaneously and randomly polymerize along the whole length of the filament and the only way of regulating the assembly is by phosphorylation. The best way of disrupting intermediate filaments is either by adding a phosphatase inhibitor (SB203580 for example) or by heat shocking cells (42C for 15mins), and other shocks (osmotic, H2O2) though these then to be reversible effects, plus the fact you disrupt other things in the process too.
If anyone has suggestions though I would interested to hear though.

Good Luck

Lost in the Lab

thank you for your suggestion;
I know about phosphatase inhibitor but i don't like it because of its unspecific effects on other cellular processes. so i'm looking for a specific drug. I read about cisplatin that induces intermediate filament reorganization without affect others cytoskeleton strucure or without induce vimentin synthesis inhibition.
I attach same papers about it.
grazie

i forgot it

There are some peptide inhibitor works published using sequences derived from one of the protein-protein interaction domain. I read it sometimes ago, but cant find it at this point.

if yuo would remember the paper where they describe the peptide inhibitor, please contact me again

Yes, I remember those papers, they used synthetic boundary sequence peptides to disrupt the existing filament network within the cells. Most of this work was done with vimentin, desmin and keratin filaments and there were some differences on the amount of peptide you add to disrupt the filaments so it might depend on your filaments that you want to work on, vimentin, GFAP are probably fine nestin, doesn't assemble with out either GFAP or vimentin so maybe fine too, I'm not sure about the neurofilaments as there's alot of crosslinking in their long CT tails and how stable they are I'm not sure.

here's one paper, there are a few more- the first Authors are Geisler et al (1993) and Goldman et al, 1996.

Thanks for the cisplatin paper, its interesting