Bio

Professional Education


  • Doctor of Philosophy, Johns Hopkins University (2009)

Stanford Advisors


Publications

Journal Articles


  • Presynaptic Neurexin-3 Alternative Splicing trans-Synaptically Controls Postsynaptic AMPA Receptor Trafficking CELL Aoto, J., Martinelli, D. C., Malenka, R. C., Tabuchi, K., Suedhof, T. C. 2013; 154 (1): 75-88

    Abstract

    Neurexins are essential presynaptic cell adhesion molecules that are linked to schizophrenia and autism and are subject to extensive alternative splicing. Here, we used a genetic approach to test the physiological significance of neurexin alternative splicing. We generated knockin mice in which alternatively spliced sequence #4 (SS4) of neuexin-3 is constitutively included but can be selectively excised by cre-recombination. SS4 of neurexin-3 was chosen because it is highly regulated and controls neurexin binding to neuroligins, LRRTMs, and other ligands. Unexpectedly, constitutive inclusion of SS4 in presynaptic neurexin-3 decreased postsynaptic AMPA, but not NMDA receptor levels, and enhanced postsynaptic AMPA receptor endocytosis. Moreover, constitutive inclusion of SS4 in presynaptic neurexin-3 abrogated postsynaptic AMPA receptor recruitment during NMDA receptor-dependent LTP. These phenotypes were fully rescued by constitutive excision of SS4 in neurexin-3. Thus, alternative splicing of presynaptic neurexin-3 controls postsynaptic AMPA receptor trafficking, revealing an unanticipated alternative splicing mechanism for trans-synaptic regulation of synaptic strength and long-term plasticity.

    View details for DOI 10.1016/j.cell.2013.05.060

    View details for Web of Science ID 000321327900011

    View details for PubMedID 23827676

  • Cerebellins meet neurexins (Commentary on Matsuda & Yuzaki) EUROPEAN JOURNAL OF NEUROSCIENCE Martinelli, D. C., Suedhof, T. C. 2011; 33 (8): 1445-1446
  • The cell-adhesion G protein-coupled receptor BAI3 is a high-affinity receptor for C1q-like proteins PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Bolliger, M. F., Martinelli, D. C., Suedhof, T. C. 2011; 108 (6): 2534-2539

    Abstract

    C1q-like genes (C1ql1-C1ql4) encode small, secreted proteins that are expressed in differential patterns in the brain but whose receptors and functions remain unknown. BAI3 protein, in contrast, is a member of the cell-adhesion class of G protein-coupled receptors that are expressed at high levels in the brain but whose ligands have thus far escaped identification. Using a biochemical approach, we show that all four C1ql proteins bind to the extracellular thrombospondin-repeat domain of BAI3 with high affinity, and that this binding is mediated by the globular C1q domains of the C1ql proteins. Moreover, we demonstrate that addition of submicromolar concentrations of C1ql proteins to cultured neurons causes a significant decrease in synapse density, and that this decrease was prevented by simultaneous addition of the thrombospondin-repeat fragment of BAI3, which binds to C1ql proteins. Our data suggest that C1ql proteins are secreted signaling molecules that bind to BAI3 and act, at least in part, to regulate synapse formation and/or maintenance.

    View details for DOI 10.1073/pnas.1019577108

    View details for Web of Science ID 000287084500066

    View details for PubMedID 21262840

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