Background: The social amoeba Dictyostelium discoideum executes a multicellular development program upon starvation. This morphogenetic process requires the differential regulation of a large number of genes and is coordinated by extracellular signals. The MADS-box transcription factor SrfA is required for several stages of development, including slug migration and spore terminal differentiation. Results: Subtractive hybridization allowed the isolation of a gene, sigN (SrfA-induced gene N), that was dependent on the transcription factor SrfA for expression at the slug stage of development. Homology searches detected the existence of a large family of sigN-related genes in the Dictyostelium discoideum genome. The 13 most similar genes are grouped in two regions of chromosome 2 and have been named Group1 and Group2 sigN genes. The putative encoded proteins are 87–89 amino acids long. All these genes have a similar structure, composed of a first exon containing a 13 nucleotides long open reading frame and a second exon comprising the remaining of the putative coding region. The expression of these genes is induced at10 hours of development. Analyses of their promoter regions indicate that these genes are expressed in the prestalk region of developing structures. The addition of antibodies raised against SigN Group 2 proteins induced disintegration of multi-cellular structures at the mound stage of development. Conclusion: A large family of genes coding for small proteins has been identified in D. discoideum. Two groups of very similar genes from this family have been shown to be specifically expressed in prestalk cells during development. Functional studies using antibodies raised against Group 2 SigN proteins indicate that these genes could play a role during multicellular development.

Microtubule-targeting agents (MTAs) represent one of the most successful first-line therapies prescribed for cancer treatment. They interfere with microtubule (MT) dynamics by either stabilizing or destabilizing MTs, and in culture, they are believed to kill cells via apoptosis after eliciting mitotic arrest, among other mechanisms. This classical view of MTA therapies persisted for many years. However, the limited success of drugs specifically targeting mitotic proteins, and the slow growing rate of most human tumors forces a reevaluation of the mechanism of action of MTAs. Studies from the last decade suggest that the killing efficiency of MTAs arises from a combination of interphase and mitotic effects. Moreover, MTs have also been implicated in other therapeutically relevant activities, such as decreasing angiogenesis, blocking cell migration, reducing metastasis, and activating innate immunity to promote proinflammatory responses. Two key problems associated with MTA therapy are acquired drug resistance and systemic toxicity. Accordingly, novel and effective MTAs are being designed with an eye toward reducing toxicity without compromising efficacy or promoting resistance. Here, we will review the mechanism of action of MTAs, the signaling pathways they affect, their impact on cancer and other illnesses, and the promising new therapeutic applications of these classic drugs.

Built to be reversible: There has been some success in designing stable peptide filaments; however, mimicking the reversible assembly of many natural protein filaments is challenging. Dynamic filaments usually comprise independently folded and asymmetric proteins and using such building blocks requires the design of multiple intermonomer interfaces. Shen et al. report the design of self-assembling helical filaments based on previously designed stable repeat proteins. The filaments are micron scale, and their diameter can be tuned by varying the number of repeats in the monomer. Anchor and capping units, built from monomers that lack an interaction interface, can be used to control assembly and disassembly. Science , this issue p. 705

Myxococcus xanthus Social (S) motility occurs at high cell densities and is powered by the extension and retraction of Type IV pili which bind ligands normally found in matrix exopolysaccharides (EPS). Previous studies showed that FrzS, a protein required for S-motility, is organized in polar clusters that show pole-to-pole translocation as cells reverse their direction of movement. Since the leading cell pole is the site of both the major FrzS cluster and type IV pilus extension/retraction, it was suggested that FrzS might regulate S-motility by activating pili at the leading cell pole. Here, we show that FrzS regulates EPS production, rather than type IV pilus function. We found that the frzS phenotype is distinct from that of Type IV pilus mutants such as pilA and pilT, but indistinguishable from EPS mutants, such as epsZ. Indeed, frzS mutants can be rescued by the addition of purified EPS, 1% methylcellulose, or co-culturing with wildtype cells. Our data also indicate that the cell density requirement in S-motility is likely a function of the ability of cells to construct functional multicellular clusters surrounding an EPS core.