Mikkel Jensen and collaborators highlighted in The Journal of Biological Chemistry

September 10, 2012

Graduate student Mikkel Herholdt Jensen and collaborators were highlighted in The Journal of Biological Chemistry for their work, “The conformational state of actin filaments regulates branching by Arp2/3 complex”.  The article was chosen by the editorial board as the JBC paper of the week for its significance and overall importance.

The work was conducted by Mikkel Herholdt Jensen (Boston University Physics Department; Moore lab) and Eliza J. Morris (Harvard University School of Engineering and Applied Science; Weitz lab), in collaboration with researchers at Boston Biomedical Research Institute and the University of Pennsylvania.

The focus of the research is actin, a cytoskeletal protein which plays a critical role in cell motility.  A cell's ability to move is driven by the assembly of monomeric actin into filaments, physically pushing on the cell membrane and forming cell protrusions at the leading edge of the cell.  The actin assembly involves actin-binding proteins, such as the actin-related protein 2/3 (Arp2/3) complex, which nucleates actin filaments and forms branched actin filament structures.  The Arp2/3 complex specifically targets newly polymerized actin at the leading edge of the cell, but the underlying mechanism for this selectivity is not well understood.  This recent work demonstrates that caldesmon, a second actin-binding protein, increases the Arp2/3-mediated branching activity when bound to newly formed actin filaments and maintains the filaments in a state of high Arp2/3 affinity.  Upon caldesmon unbinding, however, the actin transitions to a second state with low Arp2/3 complex affinity.  This presents a novel regulatory mechanism in which the tuning of the actin filament state by caldesmon regulates actin’s interactions with other binding partners.

The work can be viewed online at http://www.jbc.org/content/287/37/31447.

Example of fluorescence confocal image of actin polymerizing in the presence of Arp2/3 complex.  Actin filaments (green) were first prepolymerized either with (A) or without (B) caldesmon present.  After several hours, a second color of fluorescent monomeric actin was added and allowed to polymerize (red).  The caldesmon-decorated actin exhibited more Arp2/3-induced actin branches, indicated by white arrows.  Scale bar is 5 μm. Fluorescence confocal image of actin polymerizing in the presence of Arp2/3 complex. Actin filaments (green) were first prepolymerized either with (A) or without (B) caldesmon present. After several hours, a second color of fluorescent monomeric actin was added and allowed to polymerize (red). The caldesmon-decorated actin exhibited more Arp2/3-induced actin branches, indicated by white arrows. Scale bar is 5 microns.
Close-up fluorescence confocal image of two actin branches exhibiting the ~70° angle characteristic of Arp2/3-induced actin branches. Close-up fluorescence confocal image of two actin branches exhibiting the ~70 degree angle characteristic of Arp2/3-induced actin branches.