a multifunctional actin assembly factor, JMY, in and out of the nucleus

Nat Cell Biol. 2009 Mar 15.
p53-cofactor JMY is a multifunctional actin nucleation factor.
Zuchero JB, Coutts AS, Quinlan ME, Thangue NB, Mullins RD.

Cellular and Molecular Pharmacology, University of California, San Francisco, California 94158, USA.

Many cellular structures are assembled from networks of actin filaments, and the architecture of these networks depends on the mechanism by which the filaments are formed. Several classes of proteins are known to assemble new filaments, including the Arp2/3 complex, which creates branched filament networks, and Spire, which creates unbranched filaments. We find that JMY, a vertebrate protein first identified as a transcriptional co-activator of p53, combines these two nucleating activities by both activating Arp2/3 and assembling filaments directly using a Spire-like mechanism. Increased levels of JMY expression enhance motility, whereas loss of JMY slows cell migration. When slowly migrating HL-60 cells are differentiated into highly motile neutrophil-like cells, JMY moves from the nucleus to the cytoplasm and is concentrated at the leading edge. Thus, JMY represents a new class of multifunctional actin assembly factor whose activity is regulated, at least in part, by sequestration in the nucleus.

PMID: 19287377

This work has been presented in last year's ASCB meeting.

What does the multifunctional mean? This protein not only can activate the Arp2/3 complex, but also can directly nucleate actin. It is all hard wired in JMY's protein sequence. The C terminal 3 WH2 domains and CA domain hint its unique function ......

These two combined actin assembly promoting activities might be very important for rapid assembly of branched actin network, as the authors said "We propose that JMY contributes to cell motility by nucleating filaments to jump-start Arp2/3-dependent nucleation and branching. By first nucleating new mother filaments and then activating Arp2/3 to branch off these filaments, JMY could promote the rapid formation of a branched actin network."

Because this JMY protein was discovered as a cofactor for transcription, it will be very interesting to explore its role in bridging transcription regulation with cytoskeleton dynamics.