Nature advance online publication 27 January 2010
doi:10.1038/nature08783;
Received 4 November 2009; Accepted 5 January 2010; Published online 27 January 2010 The cells and peripheral representation of sodium taste in mice Jayaram Chandrashekar 1,4, Christina Kuhn 2,5, Yuki Oka 1,5,4, David A. Yarmolinsky 1,4, Edith Hummler 3, Nicholas J. P. Ryba 2 & Charles S. Zuker 1,4 1 Howard Hughes Medical Institute and Departments of Neurobiology and Neurosciences, University of California at San Diego, La Jolla, California 92093-0649, USA
2 National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA
3 Pharmacology and Toxicology Department, Faculty of Biology and Medicine, University of Lausanne, CH-1005 Lausanne, Switzerland
4 Present addresses: Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia 20147, USA (J.C.); Departments of Biochemistry and Molecular Biophysics and of Neuroscience, Howard Hughes Medical Institute, Columbia College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA (Y.O., D.A.Y., C.S.Z.).
5 These authors contributed equally to this work. Correspondence and requests for materials should be addressed to C.S.Z. (Email: cz2195@columbia.edu). Salt taste in mammals can trigger two divergent behavioural responses. In general, concentrated saline solutions elicit robust behavioural aversion, whereas low concentrations of NaCl are typically attractive, particularly after sodium depletion 1, 2, 3, 4, 5. Notably, the attractive salt pathway is selectively responsive to sodium and inhibited by amiloride, whereas the aversive one functions as a non-selective detector for a wide range of salts 1, 2, 3, 6, 7, 8, 9. Because amiloride is a potent inhibitor of the epithelial sodium channel (ENaC), ENaC has been proposed to function as a component of the salt-taste-receptor system 1, 3, 6, 7, 8, 9, 10, 11, 12, 13, 14. Previously, we showed that four of the five basic taste qualities—sweet, sour, bitter and umami—are mediated by separate taste-receptor cells (TRCs) each tuned to a single taste modality, and wired to elicit stereotypical behavioural responses 5, 15, 16, 17, 18. Here we show that sodium sensing is also mediated by a dedicated population of TRCs. These taste cells express the epithelial sodium channel ENaC 19, 20, and mediate behavioural attraction to NaCl. We genetically engineered mice lacking ENaCα in TRCs, and produced animals exhibiting a complete loss of salt attraction and sodium taste responses. Together, these studies substantiate independent cellular substrates for all five basic taste qualities, and validate the essential role of ENaC for sodium taste in mice.

Science 29 January 2010:
Vol. 327. no. 5965, pp. 547 – 552
DOI: 10.1126/science.1179735 Local and Long-Range Reciprocal Regulation of cAMP and cGMP in Axon/Dendrite Formation Maya Shelly 1,* Byung Kook Lim 1,* Laura Cancedda 1,2 Sarah C. Heilshorn 1, Hongfeng Gao 1, Mu-ming Poo 1 Cytosolic cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) often mediate antagonistic cellular actions of extracellular factors, from the regulation of ion channels to cell volume control and axon guidance. We found that localized cAMP and cGMP activities in undifferentiated neurites of cultured hippocampal neurons promote and suppress axon formation, respectively, and exert opposite effects on dendrite formation. Fluorescence resonance energy transfer imaging showed that alterations of the amount of cAMP resulted in opposite changes in the amount of cGMP, and vice versa, through the activation of specific phosphodiesterases and protein kinases. Local elevation of cAMP in one neurite resulted in cAMP reduction in all other neurites of the same neuron. Thus, local and long-range reciprocal regulation of cAMP and cGMP together ensures coordinated development of one axon and multiple dendrites. 1 Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720, USA.
2 Department of Neuroscience and Brain Technologies, Italian Institute of Technology, Via Morego 30, Genoa 16163, Italy.
* These authors contributed equally to this work. Present address: Department of Materials Science and Engineering, Geballe Laboratory for Advanced Materials, Stanford University, Stanford, CA 94305, USA. To whom correspondence should be addressed. E-mail: mpoo@uclink.berkeley.edu

A key part of the life cycle of the malaria parasite — and the one that makes transmission via the mosquito to other hosts possible — involves a period of growth inside host red blood cells. During this phase the Plasmodium cells export several hundred proteins into the host blood cell, which they remodel as an environment suitable for parasite multiplication. Proteins destined for export contain a conserved motif called PEXEL, and when this is cleaved in the endoplasmic reticulum the protein can translocate into the host cell. Two independent studies now reveal the identity of the enzyme that cleaves the PEXEL motif as the aspartyl protease plasmepsin V. This finding immediately suggests that plasmepsin V is a potential drug target for antimalarial agents.

Mol Biochem Parasitol. 2008 Aug;160(2):107-15. Epub 2008 May 2. N-terminal processing of proteins exported by malaria parasites. Chang HH, Falick AM, Carlton PM, Sedat JW, DeRisi JL, Marletta MA. Department of Chemistry, University of California, Berkeley, CA 94720, USA. Malaria parasites utilize a short N-terminal amino acid motif termed the Plasmodium export element (PEXEL) to export an array of proteins to the host erythrocyte during blood stage infection. Using immunoaffinity chromatography and mass spectrometry, insight into this signal-mediated trafficking mechanism was gained by discovering that the PEXEL motif is cleaved and N-acetylated. PfHRPII and PfEMP2 are two soluble proteins exported by Plasmodium falciparum that were demonstrated to undergo PEXEL cleavage and N-acetylation, thus indicating that this N-terminal processing may be general to many exported soluble proteins. It was established that PEXEL processing occurs upstream of the brefeldin A-sensitive trafficking step in the P. falciparum secretory pathway, therefore cleavage and N-acetylation of the PEXEL motif occurs in the endoplasmic reticulum (ER) of the parasite. Furthermore, it was shown that the recognition of the processed N-terminus of exported proteins within the parasitophorous vacuole may be crucial for protein transport to the host erythrocyte. It appears that the PEXEL may be defined as a novel ER peptidase cleavage site and a classical N-acetyltransferase substrate sequence. PMID: 18534695

Nature 463, 627-631 (4 February 2010)
doi:10.1038/nature08728;
Received 30 July 2009; Accepted 4 December 2009 An aspartyl protease directs malaria effector proteins to the host cell Justin A. Boddey 1, Anthony N. Hodder 1, Svenja Günther 1, Paul R. Gilson 2, Heather Patsiouras 3, Eugene A. Kapp 3, J.

Nature advance online publication 27 January 2010
doi:10.1038/nature08797 Direct conversion of fibroblasts to functional neurons by defined factors Thomas Vierbuchen 1,2, Austin Ostermeier 1,2, Zhiping P. Pang 3, Yuko Kokubu 1, Thomas C. Südhof 3,4 & Marius Wernig 1,2 1 Institute for Stem Cell Biology and Regenerative Medicine, Department of Pathology,
2 Program in Cancer Biology,
3 Department of Molecular and Cellular Physiology,
4 Howard Hughes Medical Institute, Stanford University School of Medicine, 1050 Arastradero Road, Palo Alto, California 94304, USA Correspondence and requests for materials should be addressed to M.W. (Email: wernig@stanford.edu). Cellular differentiation and lineage commitment are considered to be robust and irreversible processes during development. Recent work has shown that mouse and human fibroblasts can be reprogrammed to a pluripotent state with a combination of four transcription factors. This raised the question of whether transcription factors could directly induce other defined somatic cell fates, and not only an undifferentiated state. We hypothesized that combinatorial expression of neural-lineage-specific transcription factors could directly convert fibroblasts into neurons. Starting from a pool of nineteen candidate genes, we identified a combination of only three factors, Ascl1, Brn2 (also called Pou3f2) and Myt1l, that suffice to rapidly and efficiently convert mouse embryonic and postnatal fibroblasts into functional neurons in vitro. These induced neuronal (iN) cells express multiple neuron-specific proteins, generate action potentials and form functional synapses. Generation of iN cells from non-neural lineages could have important implications for studies of neural development, neurological disease modelling and regenerative medicine.