brate rod cells of the retina has been shown to be the chromo-

Bacterial cells in their native environments must cope with factors that compromise the integrity of the cell. The mechanisms of coping with damage in a social or multicellular context are poorly understood. Here we investigated how a model social bacterium, Myxococcus xanthus, approaches this problem. We focused on the social behavior of outer membrane exchange (OME), in which cells transiently fuse and exchange their outer membrane (OM) contents. This behavior requires TraA, a homophilic cell surface receptor that identifies kin based on similarities in a polymorphic region, and the TraB cohort protein. As observed by electron microscopy, TraAB overexpression catalyzed a prefusion OM junction between cells. We then showed that damage sustained by the OM of one population was repaired by OME with a healthy population. Specifically, LPS mutants that were defective in motility and sporulation were rescued by OME with healthy donors. In addition, a mutant with a conditional lethal mutation in lpxC, an essential gene required for lipid A biosynthesis, was rescued by Tradependent interactions with a healthy population. Furthermore, lpxC cells with damaged OMs, which were more susceptible to antibiotics, had resistance conferred to them by OME with healthy donors. We also show that OME has beneficial fitness consequences to all cells. Here, in merged populations of damaged and healthy cells, OME catalyzed a dilution of OM damage, increasing developmental sporulation outcomes of the combined population by allowing it to reach a threshold density. We propose that OME is a mechanism that myxobacteria use to overcome cell damage and to transition to a multicellular organism.Myxococcus xanthus | outer membrane | lipopolysaccharide | lpxC | fusion A fundamental question in biology is how cells cope with damage. Microbes occupy diverse habitats fraught with physical, biological, and chemical insults (1, 2). UV radiation, desiccation, predation, extracellular enzymes, antimicrobial compounds, pH, temperature, and osmolarity changes are all stresses to the individual cell. In addition, when cells are in nutrient-poor environments, cell division can be rare, taking days to months to complete (3). In a slow-growing state, cell-surface components that may not be undergoing active repair can accumulate damage through natural aging processes such as oxidation (4, 5) and protein denaturation. Although internal cell stress response pathways are known (6), mechanisms to cope with cell surface damage are less well understood.Although cell damage threatens the fitness of the individual, social organisms have strength in numbers. The strategy of kin selection allows evolutionarily viable cooperation between individuals in a closely related population (7). Communication between individuals and sharing of resources establishes the potential for assistance between individual population members. Social support can be beneficial when the fitness of individuals in a group depends on collaborative behaviors such as prey hunting or the developm...

Chronic infection with hepatitis B virus (HBV) is associated with an increased risk for the development of cirrhosis and hepatocellular carcinoma (HCC).C hronic hepatitis B virus (HBV) infection is one of the major etiologic factors in the development of hepatocellular carcinoma (HCC). 1,2 Epidemiologic studies have shown that chronic HBV-infection is associated with a 100-fold increase in the risk for HCC development relative to noncarriers, placing HBV in the forefront among known human carcinogens. 3,4 Several lines of evidence suggest that HBV is tolerated by infected hepatocytes that do not show overt pathogenic reactions to virus replication. Therefore, liver damage observed in acute or chronic hepatitis B infection is mainly caused by cellular immune responses, which play a key role in the control of HBV infection. 5 Continuous necrosis and liver cell regeneration in the inflammatory context provide the driving force for carcinogenic progression in HBV carrier livers by allowing the selection of mutated hepatocytes. The long latency period for the development of HCC reveals a multistaged mechanism, in which selection of progressively mutated hepatocytes occurs. Moreover, virus-host interactions have been related to the oncogenic properties of the virus. Tumor progression may also be promoted by the presence of viral gene products, such as the X protein, 6-8 or by overexpression and accumulation of the large envelope protein. 9 The inappropriate expression of a truncated form of the middle envelope protein produced from integrated viral sequences has also been reported. 10 A direct role for integration of a mammalian hepadnavirus in the development of HCC has been identified for the woodchuck hepatitis virus (WHV). Integrations of WHV DNA into the N-myc and c-myc protooncogenes have shown that WHV integration can activate cellular protooncogenes by enhancer or promoter insertion. 11,12 Molecular analysis of genomic DNA from human HCCs revealed the presence of clonally propagated viral DNA integrations and the majority of tumors from chronic HBV carriers harbor integrated viral DNA, often multiple copies per cell. [13][14][15][16] Although a cellular protooncogene that is commonly activated by HBV has not been identified, the high prevalence of HBV integrations at sites of chromosomal abnormalities, such as deletions, duplications, and chromosomal translocations, has suggested that the integration process may occur in a manner that promotes mutagenesis. 1,17,18 Studies on the natural history of integrations of duck hepatitis B virus (DHBV) have directly shown that hepadnavirus integrations

Golgin-160 is a ubiquitously expressed peripheral Golgi membrane protein that is important for transduction of certain pro-apoptotic signals at the Golgi complex. However, the role of golgin-160 in normal Golgi structure and function is unknown. Here, we show that depletion of golgin-160 using RNA interference (RNAi) does not affect Golgi morphology or constitutive membrane traffic in HeLa cells. However, depletion of golgin-160 leads to significantly decreased cell surface levels of exogenously expressed b1-adrenergic receptor (b1AR), which can be rescued by expression of RNAi-resistant forms of golgin-160. Furthermore, overexpression of golgin-160 leads to higher surface levels of b1AR. Golgin-160 is localized mostly in the cis and medial regions of the Golgi stack by immunoelectron microscopy, suggesting that it does not directly promote incorporation of b1AR into transport vesicles at the trans Golgi network. Golgin-160 interacts with b1AR in vitro, and we mapped the interaction to a region between residues 140 and 257 in the head of golgin-160 and the third intracellular loop of b1AR. Our results support the idea that golgin-160 may promote efficient surface delivery of a subset of cargo molecules.