SUMMARY Cellular differentiation, mating, and filamentous growth are regulated in many fungi by environmental and nutritional signals. For example, in response to nitrogen limitation, diploid cells of the yeast Saccharomyces cerevisiae undergo a dimorphic transition to filamentous growth referred to as pseudohyphal differentiation. Yeast filamentous growth is regulated, in part, by two conserved signal transduction cascades: a mitogen-activated protein kinase cascade and a G-protein regulated cyclic AMP signaling pathway. Related signaling cascades play an analogous role in regulating mating and virulence in the plant fungal pathogen Ustilago maydis and the human fungal pathogens Cryptococcus neoformans and Candida albicans. We review here studies on the signaling cascades that regulate development of these and other fungi. This analysis illustrates both how the model yeast S. cerevisiae can serve as a paradigm for signaling in other organisms and also how studies in other fungi provide insights into conserved signaling pathways that operate in many divergent organisms.

, 1a, 2a, 2b, 3a, 4a, 5b, X, and Y, found that all belong to a new sequence type (ST), ST91. Pulsed-field gel electrophoresis revealed 154 pulse types with 655 S. flexneri isolates analyzed and identified 57 serotype switching events. The data suggest that S. flexneri epidemics in China have been caused by a single epidemic clone, ST91, with frequent serotype switching to evade infection-induced immunity to serotypes to which the population was exposed previously. The clone has also acquired resistance to multiple antibiotics. These findings underscore the challenges to the current vaccine development and control strategies for shigellosis.

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The first invertebrate intestinal mucin, termed insect intestinal mucin (IIM), was recently identified from Trichoplusia ni larvae (Wang, P., and Granados, R. R. (1997) Proc. Natl. Acad. Sci. U. S. A., in press). We report the cDNA cloning and sequencing of IIM, which is only the second completely sequenced intestinal mucin after human intestinal mucin, MUC2. To clone and sequence the cDNA for IIM, a T. ni larval midgut cDNA expression library was constructed and screened with an anti-IIM antiserum. Two full-length cDNA clones for IIM were identified and sequenced. The deduced proteins from the two cDNA clones contained 807 and 788 amino acid residues, respectively. The structural organization of IIM is similar to that of MUC2, containing a 25-amino acid signal leading sequence and two threonine/proline/ alanine-rich tandem repeat domains flanked by cysteine-rich sequences. One tandem repeat domain contained two repeating units, TTTQAP and AATTP, and the other contained one repeating unit, TAAP. The cysteine-rich regions showed potential chitin binding features. By immunolocalization in tissue sections, it was determined that IIM is expressed in midgut tissues. The IIM mRNA is abundant in the midgut tissue, and Northern blot analysis indicated that IIM transcripts were not polydispersed as is found in mammalian mucin transcription.

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Neutrophils are important in innate immunity and acute inflammatory responses. However, the regulation of their recruitment to sites of inflammation has not been well characterized. Here, we investigated the kinase PIP5K1C and showed that PIP5K1C-deficiency impaired neutrophil recruitment due to an adhesion defect. PIP5K1C regulated the adhesion through facilitating RhoA GTPase and integrin activation by chemoattractants. Integrins could induce an isoform of PIP5K1C, PIP5K1C-90, polarization in neutrophils through intracellular vesicle transport independently of exogenous chemoattractant. PIP5K1C-90 polarization was required for polarized RhoA activation at uropods and provided an initial directional cue for neutrophil polarization on the endothelium. Importantly, the polarization was also required for circumventing the inhibition of lamellipodium formation by RhoA so that neutrophils could form leading edges required for transendothelial migration. Because integrins are not known to regulate neutrophil polarization, our study revealed a previously underappreciated role of integrin signaling in neutrophil regulation.

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