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Local Arp2/3 dependent actin assembly modulates applied traction force during apCAM adhesion site maturation
(2017)Molecular Biology of the CellHomophilic binding of immunoglobulin superfamily molecules such as the Aplysia cell adhesion molecule (apCAM) leads to actin filament assembly near nascent adhesion sites. Such actin assembly can generate significant localized forces that have not been characterized in the larger context of axon growth and guidance. We used apCAM-coated bead substrates applied to the surface of neuronal growth cones to characterize the development of ...Journal Article -
Molecular basis of Kar9-Bim1 complex function during mating and spindle positioning
(2016)Molecular Biology of the CellThe Kar9 pathway promotes nuclear fusion during mating and spindle alignment during metaphase in budding yeast. How Kar9 supports the different outcome of these two divergent processes is an open question. Here, we show that three sites in the C-terminal disordered domain of Kar9 mediate tight Kar9 interaction with the C-terminal dimerization domain of Bim1 (EB1 orthologue). Site1 and Site2 contain SxIP motifs; however, Site3 defines a ...Journal Article -
Nanoscopic compartmentalization of membrane protein motion at the axon initial segment
(2016)The Journal of Cell BiologyThe axon initial segment (AIS) is enriched in specific adaptor, cytoskeletal, and transmembrane molecules. During AIS establishment, a membrane diffusion barrier is formed between the axonal and somatodendritic domains. Recently, an axonal periodic pattern of actin, spectrin, and ankyrin forming 190-nm-spaced, ring-like structures has been discovered. However, whether this structure is related to the diffusion barrier function is unclear. ...Journal Article -
Standardized benchmarking in the quest for orthologs
(2016)Nature MethodsAchieving high accuracy in orthology inference is essential for many comparative, evolutionary and functional genomic analyses, yet the true evolutionary history of genes is generally unknown and orthologs are used for very different applications across phyla, requiring different precision–recall trade-offs. As a result, it is difficult to assess the performance of orthology inference methods. Here, we present a community effort to establish ...Journal Article -
Inferring causal molecular networks: empirical assessment through a community-based effort
(2016)Nature MethodsIt remains unclear whether causal, rather than merely correlational, relationships in molecular networks can be inferred in complex biological settings. Here we describe the HPN-DREAM network inference challenge, which focused on learning causal influences in signaling networks. We used phosphoprotein data from cancer cell lines as well as in silico data from a nonlinear dynamical model. Using the phosphoprotein data, we scored more than ...Journal Article -
Abnormal Intermediate Filament Organization Alters Mitochondrial Motility in Giant Axonal Neuropathy Fibroblasts
(2016)Molecular Biology of the CellGiant axonal neuropathy (GAN) is a rare disease caused by mutations in the GAN gene, which encodes gigaxonin, an E3 ligase adapter that targets intermediate filament (IF) proteins for degradation in numerous cell types, including neurons and fibroblasts. The cellular hallmark of GAN pathology is the formation of large aggregates and bundles of IFs. In this study, we show that both the distribution and motility of mitochondria are altered ...Journal Article -
Analysis of the Protein Kinase A-Regulated Proteome of Cryptococcus neoformans Identifies a Role for the Ubiquitin-Proteasome Pathway in Capsule Formation
(2016)mBioThe opportunistic fungal pathogenCryptococcus neoformanscauses life-threatening meningitis in immunocompro-mised individuals. The expression of virulence factors, including capsule and melanin, is in part regulated by the cyclic-AMP/protein kinase A (cAMP/PKA) signal transduction pathway. In this study, we investigated the influence of PKA on the composi-tion of the intracellular proteome to obtain a comprehensive understanding of the ...Journal Article -
The bee microbiome: Impact on bee health and model for evolution and ecology of host-microbe interactions
(2016)mBioAs pollinators, bees are cornerstones for terrestrial ecosystem stability and key components in agricultural productivity. All animals, including bees, are associated with a diverse community of microbes, commonly referred to as the microbiome. The bee microbiome is likely to be a crucial factor affecting host health. However, with the exception of a few pathogens, the impacts of most members of the bee microbiome on host health are poorly ...Journal Article -
Spontaneous and electric feld-controlled front-rear polarization of human keratinocytes
(2015)Molecular Biology of the CellIt has long been known that electrical fields (EFs) are able to influence the direction of migrating cells, a process commonly referred to as electrotaxis or galvanotaxis. Most studies have focused on migrating cells equipped with an existing polarity before EF application, making it difficult to delineate EF-specific pathways. Here we study the initial events in front–rear organization of spreading keratinocytes to dissect the molecular ...Journal Article -
Reproducible quantitative proteotype data matrices for systems biology
(2015)Molecular Biology of the CellHistorically, many mass spectrometry–based proteomic studies have aimed at compiling an inventory of protein compounds present in a biological sample, with the long-term objective of creating a proteome map of a species. However, to answer fundamental questions about the behavior of biological systems at the protein level, accurate and unbiased quantitative data are required in addition to a list of all protein components. Fueled by ...Journal Article