Yale/NIDA Neuroproteomics Center Publications

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Journal of Neuroscience, 2014
Cover legend: Artistic rendition of αβγ-synuclein knockout synapses, showing a deficit in cholera toxin-HRP positive vesicles (black vesicles). This experiment in synuclein-null neurons supports a physiological role for α-synuclein in synaptic vesicle endocytosis. For more information see the article by Vargas, K.J., Makhani, S., Davis, T., Westphal, C., Castillo, P.E., and Chandra, S.S. (2014). Synucleins regulate the kinetics of synaptic vesicle endocytosis. J. Neuroscience 34(28), 9364-9376. (PMCID: PMC4087213)
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Journal of Cell Biology, 2012
Cover legend: GFP-Farp1 (green) promotes the polymerization of F-actin (red) in dendritic spines, the postsynaptic protrusions of excitatory synapses. Cheadle and Biederer reveal that Farp1 works with the synaptic adhesion molecule SynCAM 1 to promote spine assembly and organize presynaptic active zones. The postsynaptic marker Shank is stained blue. For more information see the article by Cheadle, L., Biederer, T. (2012) The novel synaptogenic protein Farp1 links postsynaptic cytoskeletal dynamics and transsynaptic organization. J Cell Biol. 199(6):985-1001. (PMCID: PMC3518221)
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Journal of Biological Chemistry, 2010
Cover legend: SynCAM adhesion molecules connect pre- and postsynaptic membranes to organize synapses. The cover image shows a SynCAM 2 homodimer (left) and a SynCAM 1/2 heterodimer (right) based on the crystal structure and crystal packing of the first SynCAM 2 immunoglobulin domain. The strength of these trans-synaptic interactions is modulated by N-glycans (red) that reduce SynCAM 2 adhesion, likely through steric hindrance. In contrast, N-glycans (brown) facing away from SynCAM 1 may restrict its conformational freedom and position it toward binding. For more information see the article by Fogel, A.I., Li, Y., Wang, Q., Lam, T.T., Modis, Y. and Biederer, T. (2010) N-Glycosylation at the SynCAM immunoglobulin interface modulates synaptic adhesion. J. Biol. Chem. 285: 34864-34874. (PMCID: PMC2966101)
Cell, 2009
Cover legend: K-Cl cotransporters (KCCs) control transmembrane electrolyte flux in a variety of physiologic settings, including the acute response to altered extracellular osmolarity. In this issue of Cell, Rinehart et al. (pp. 525–536) use targeted phosphoproteomics to reveal how phosphorylation at two conserved sites in KCCs controls their activity. The image depicts the activation of KCC3 in red blood cells in response to extracellular hypotonicity. KCC3 (blue) is shown embedded in the red blood cell membrane. Cotransporters that are phosphorylated at T991 and T1048 in the C terminus (highlighted in a white “flash”) are inactive, while those that are dephosphorylated at these sites are active, allowing K-Cl efflux from the cell and preventing cell swelling due to influx of water. For more information see the article by Rinehart, J., Maksimova, Y.D., Tanis, J.E., Stone, K.E., Hodson, C.A., Zhang, J, Risinger, M., Pan, W., Wu, D., Colangelo, C.M., Forbush, B., Joiner, C.H., Gulcicek, E.E., Gallagher, P.G., and Lifton, R.P. (2009) Sites of regulated phosphorylation that control K-Cl cotransporter activity. Cell. 138(3):525-36. (PMCID: PMC2811214)