Human-associated microbial communities vary across individuals: possible contributing factors include (genetic) relatedness, diet, and age. However, our surroundings, including individuals with whom we interact, also likely shape our microbial communities. To quantify this microbial exchange, we surveyed fecal, oral, and skin microbiota from 60 families (spousal units with children, dogs, both, or neither). Household members, particularly couples, shared more of their microbiota than individuals from different households, with stronger effects of co-habitation on skin than oral or fecal microbiota. Dog ownership significantly increased the shared skin microbiota in cohabiting adults, and dog-owning adults shared more ‘skin’ microbiota with their own dogs than with other dogs. Although the degree to which these shared microbes have a true niche on the human body, vs transient detection after direct contact, is unknown, these results suggest that direct and frequent contact with our cohabitants may significantly shape the composition of our microbial communities.DOI: http://dx.doi.org/10.7554/eLife.00458.001

Targeting of most nuclear proteins to the cell nucleus is initiated by interaction between the classical nuclear localization signals (NLSs) contained within them and the importin NLS receptor complex. We have recently delineated a novel 38 amino acid transport signal in the hnRNP A1 protein, termed M9, which confers bidirectional transport across the nuclear envelope. We show here that M9-mediated nuclear import occurs by a novel pathway that is independent of the well-characterized, importin-mediated classical NLS pathway. Additionally, we have identified a specific M9-interacting protein, termed transportin, which binds to wild-type M9 but not to transport-defective M9 mutants. Transportin is a 90 kDa protein, distantly related to importin beta, and we show that it mediates the nuclear import of M9-containing proteins. These findings demonstrate that there are at least two receptor-mediated nuclear protein import pathways. Furthermore, as hnRNP A1 likely participates in mRNA export, it raises the possibility that transportin is a mediator of this process as well.

tors by the specific names used in their original descriptions. These receptors are generally large (90-130 kDa) Philadelphia, Pennsylvania 19104-6148 acidic proteins sharing 15%-25% sequence identity within a given organism. They all have an N-terminal RanGTP-binding domain, a C-terminal cargo-binding Eukaryotic cells are equipped with a machinery charged domain, and the capacity to bind components of the with the responsibility of transporting a vast number of NPC (Figure 1A). molecules in and out of the nucleus in a rapid, accurate, Many classes of cargo contain signals that bind diand often regulated manner. The cargos for this machinrectly to a cognate receptor, but three types have signals ery are diverse, comprising proteins and more elaborate that bind to the importin ␤ receptor indirectly, via adap-RNA-protein complexes (RNPs). Although the extent tor proteins. These are proteins with classical basic and complexity of trafficking between the nucleus and NLSs (either simple or bipartite) that bind the importin the cytoplasm have long been appreciated, it is only ␣ family of adaptors (Dingwall and Laskey, 1998; Gorlich, relatively recently that some of the molecular mecha-1998; Weis, 1998), U snRNAs that bind the snurportin nisms involved have been uncovered. adaptor (Huber et al., 1998; Palacios et al., 1997), and Proteins and some RNPs that need to move between replication protein A that binds the RIP␣ adaptor (Jullien the nucleus and cytoplasm in order to perform their et al., 1999). As all adaptor-utilizing cargos identified so normal cell functions are most often recognized by solufar are imported by the importin ␤ receptor, they share an ble proteins, the nuclear transport receptors. These re-N-terminal importin ␤-binding (IBB) domain (Figure 1B). ceptors mediate translocation of cargos through the A variation of the simple receptor-import cargo mechnuclear pore complex (NPC), the route for all macromoanism is illustrated by the import of histone H1. This is lecular traffic across the nuclear membrane. After demediated by a dimeric complex of two receptors, impositing their cargos in the appropriate compartment, portin ␤ and importin 7, in which importin 7 behaves like the unloaded receptors shuttle back through the NPC an adaptor or coreceptor (Jakel et al., 1999). Importin 7 to pick up more cargo. Like many vectorial cellular procan exist in either coreceptor or receptor mode, and as cesses, directionality is imposed on nucleocytoplasmic a receptor it functions in ribosomal protein import (Jakel traffic (at least in part) by a nucleotidase, the small and Gorlich, 1998). This phenomenon of receptors func-GTPase Ran.tioning in pairs might not be a quirk of importin 7: another Several experimental approaches, including in vitro receptor family member, importin 8, heterodimerizes import and export assays in higher eukaryotic cells, in with importin ␤, although a cargo for this complex has vivo transport studies in frog oocytes and yeast genetyet to be identified (Jakel et al., 1999). ics, have been ins...