Protein citrullination (a.k.a. deimination) is a novel arginine-directed post-translational modification (PTM) that results in a permanent change in the targeted protein. PeptidylArginine Deiminases (PADs) mediate the calcium-dependent deimination of the guanidino group of Arginine side chains to form an ureido group and the non-standard amino acid citrulline.

Some biologically relevant proteins known to be citrullinated include Keratin, Filaggrin, Trichohyalin, Vimentin, Myelin Basic Protein (MBP), Histones, alpha-Enolase, Fibrinogen, Fibrins, Collagen type I and II, beta-Actin, and Tubulin 9-11… It is noteworthy that several of these proteins are part of the cytoskeleton and/or are structural in nature.

Citrullination of peptidyl-arginine by peptidylarginine deiminases (PADs).

In their October newsletter, Cytoskeleton Inc. presents an overview about the consequences of citrullination, especially referring to cytoskeleton proteins such as Vimentin.

Interested in this exciting new PTM mechanism?

Download your free copy of the review:
Citrullination: Taking the Charge out of Arg

Cytoskeleton modeling molecules are relevant when trying to improve one’s understanding of cytoskeletal molecular modeling and associated mechanisms. Together with actin binding proteins, tubulin-based assays, small GTPase activation assays etc… these reagents are called small molecules, but they remain extremely potent in in vitro cell-based assays. Here, let’s take look at a selection of the most popular chemicals modifying actin or microtubule polymerization.

#1- Docetaxel

An antimitotic chemotherapeutic acting on the centrosome of the mitotic spindle via reversible high-affinity binding to microtubules. Docetaxel induces apoptosis in a variety of cancer cell lines.

#2- Epothilone B

A tubulin polymerization promoter inducing G2-M cell cycle arrest stabilizing microtubules and displaying potent cytotoxic activity in a variety of cell lines and mouse models.

#3- Latrunculins

Potent actin polymerization inhibitor disrupting microfilament organization.

#4- Nocodazole

A microtubule polymerization inhibitor used to induce mitotic arrest and cell synchronization. Nocodazol inhibits a number of cancer-related kinases including ABL, c-Kit, BRAF, MEK1, MEK2, and MET.

#5- Taxol

A chemotherapeutic agent for the treatment of breast, non-small cell lung and ovarian cancer. Taxol promotes tubulin polymerization, stabilizes microtubules in vitro and in vivo resulting in arrest of cells in the G2 and M phase of the cell cycle.

Many other well-qualified cytoskeleton modulators (Ansamitocin P-3, Cytochalasins, Colchicine, Vinblastine sulfate…) are available from various sources (my preference going to Focus Biomolecules for quality and price advantages!). Nevertheless, the 5 described here are among those most spontaneously cited by researchers.

What about you? Which ones would you recommend to study cytoskeleton dynamics?

In the past, molecular motor proteins like kinesins have been investigated with macromolecular approaches. Recent research on kinesins has been focused on resolving how kinesin is regulated by intramolecular dynamics.