A human MAP kinase interactome.

Mitogen-activated protein kinase (MAPK) pathways form the backbone of signal transduction in the mammalian cell. Here we applied a systematic experimental and computational approach to map 2,269 interactions between human MAPK-related proteins and other cellular machinery and to assemble these data into functional modules. Multiple lines of evidence including conservation with yeast supported a core network of 641 interactions. Using small interfering RNA knockdowns, we observed that approximately one-third of MAPK-interacting proteins modulated MAPK-mediated signaling. We uncovered the Na-H exchanger NHE1 as a potential MAPK scaffold, found links between HSP90 chaperones and MAPK pathways and identified MUC12 as the human analog to the yeast signaling mucin Msb2. This study makes available a large resource of MAPK interactions and clone libraries, and it illustrates a methodology for probing signaling networks based on functional refinement of experimentally derived protein-interaction maps

Cell Type-Specific Neuroprotective Activity of Untranslocated Prion Protein

Background: A key pathogenic role in prion diseases was proposed for a cytosolic form of the prion protein (PrP). However, it is not clear how cytosolic PrP localization influences neuronal viability, with either cytotoxic or anti-apoptotic effects reported in different studies. The cellular mechanism by which PrP is delivered to the cytosol of neurons is also debated, and either retrograde transport from the endoplasmic reticulum or inefficient translocation during biosynthesis has been proposed. We investigated cytosolic PrP biogenesis and effect on cell viability in primary neuronal cultures from different mouse brain regions. Principal Findings: Mild proteasome inhibition induced accumulation of an untranslocated form of cytosolic PrP in cortical and hippocampal cells, but not in cerebellar granules. A cyclopeptolide that interferes with the correct insertion of the PrP signal sequence into the translocon increased the amount of untranslocated PrP in cortical and hippocampal cells, and induced its synthesis in cerebellar neurons. Untranslocated PrP boosted the resistance of cortical and hippocampal neurons to apoptotic insults but had no effect on cerebellar cells. Significance: These results indicate cell type-dependent differences in the efficiency of PrP translocation, and argue that cytosolic PrP targeting might serve a physiological neuroprotective function

The evolutionary significance of polyploidy

Polyploidy, or the duplication of entire genomes, has been observed in prokaryotic and eukaryotic organisms, and in somatic and germ cells. The consequences of polyploidization are complex and variable, and they differ greatly between systems (clonal or non-clonal) and species, but the process has often been considered to be an evolutionary 'dead end'. Here, we review the accumulating evidence that correlates polyploidization with environmental change or stress, and that has led to an increased recognition of its short-term adaptive potential. In addition, we discuss how, once polyploidy has been established, the unique retention profile of duplicated genes following whole-genome duplication might explain key longer-term evolutionary transitions and a general increase in biological complexity

Comparison of palaeobotanical observations with experimental data on the leaf anatomy of durmast oak [Quercus petraea (Fagaceae)] in response to environmental change

To test whether stomatal density measurements on oak leaf remains are reliable tools for assessing palaeoatmospheric carbon dioxide concentration [CO2], under changing Late Miocene palaeoenvironmental conditions, young seedings of oak (Quercus petraea, Liebl.) were grown at elevated vs. ambient atmospheric [CO2] and at high humidity combined with an increased air temperature. The leaf anatomy of the young oaks was compared with that of fossil leaves of the same species. In the experiments, stomatal density and stomatal index were significantly decreased at elevated [CO2] in comparison to ambient [CO2]. Elevated [CO2] induced leaf cell expansion and reduced the intercellular air space by 35%. Leaf cell size or length were also stimulated at high air humidity and temperature. Regardless of a temperate or subtropical palaeoclimate, leaf cell size in fossil oak was not enhanced, since neither epidermal cell density nor length of the stomatal apparatus changed. The absence of these effects may be attributed to the phenological response of trees to climatic changes that balanced temporal changes in environmental variables to maintain leaf growth under optimal and stable conditions. Quercus petraea, which evolved under recurring depletions in the palaeoatmospheric [CO2], may possess sufficient phenotypic plasticity to alter stomatal frequency in hypostomatous leaves allowing high maximum stomatal conductance and high assimilation rates during these phases of low [CO2]. (C) 1998 Annals of Botany Company