Staying in the Fold
A cell's proteins are continually subjected to stresses that could promote their misfolding and aggregation. In addition, a wide variety of diseases are caused by the misfolding and aggregation of key proteins. Balch et al. (p. 916) now review the so-called proteostasis machinery, which the cell uses to combat these problems. The authors highlight the potential for manipulation of the proteostasis machinery in future efforts to treat misfolding diseases.
Getting a Handle on HIV Host Factors
Because the HIV-1 virus encodes only a handful of its own proteins, it must exploit multiple host cell processes to ensure completion of its life-cycle. Thus, many potential host factors could influence HIV infection, which for the most part remain unknown. Brass et al. (p. 921, published online 10 January; see the 11 January news story by Cohen) used a genome-wide small interfering RNA functional screen to identify a large number of HIV-dependency factors, some known, but many unknown. Several of the genes were studied further and played roles in viral entry, integration, biosynthesis, and assembly, as well as in the later stages of infection.
Cadherins on the Road to Multicellularity
How early organisms made the transition from unicellularity to multicellularity is unknown, although certain genes have been implicated as important players in this process. One such group is the cadherin family of genes that function in cell adhesion and cell-cell signaling. By examining the genome of the unicellular choanoflagellate Monosiga brevicollis, Abedin and King (p. 946) show that the genome of M. brevicollis contains 23 expressed cadherin genes--as many as several multicellular animals. At least two of the cadherins localized to the actin-filled microvilli of the protozoan feeding collar, where they may participate in the recognition and capture of bacterial prey.
Filtering Out the Bad from the Less Bad
Maternally inherited mitochondrial DNA (mtDNA) mutations are implicated in a variety of human diseases including cardiomyopathy and neurodegenerative disorders. It has been assumed that mtDNA mutations are randomly segregated by genetic drift within the female germline. Fan et al. (p. 958; see the Perspective by Shoubridge and Wai) created a sophisticated mouse model that allowed them to monitor the fates and phenotypic effects of mtDNAs containing mutations of varying severity. Surprisingly, the most pathogenic mtDNA mutation was quickly eliminated from the female germline, whereas a moderately deleterious mtDNA mutation continued to be transmitted through multiple generations. Thus, the female germline filters out the most deleterious mtDNA mutations prior to conception, thereby minimizing their impact on population fitness.
Full Metal Abscess
Tissue abscesses form when bacteria meet cells of the immune system, most notably neutrophils. Corbin et al. (p. 962; see the Perspective by Novick) now find that the abundant neutrophil protein, calprotectin, protects the host against bacterial growth by chelating metal ions used by the bacteria as nutrients. In mice during bacterial infection, calprotectin was localized to tissue abscesses where it chelated manganese and zinc ions. Infected mice lacking calprotectin had elevated metal levels and increased bacterial growth in tissue abscesses.
CAR edited in February 20, 2008
