Dr. Bryen Jordan

Exploring synaptic function and activity-dependent synapse-to-nucleus signaling

One of the principal questions in neuroscience is how does neuronal activity alter synaptic transmission. This question is critically important since activity-dependent changes in neurotransmission regulate higher order brain functions such as learning and memory. Our lab is interested in understanding how do transient changes in synaptic neurotransmission become long-term. Specifically we are interested in exploring activity-dependent synapse-to-nucleus signaling in neurons. The activity-dependent regulation of nuclear functions is essential for the long-term maintenance of synaptic strengthening and the long-term storage of memories. While the nature of this signaling pathway is widely debated, it is well known that neuronal activity results in the rapid nuclear accumulation of many proteins, including AIDA-1, Jacob, NFATc4 and NF-kB, suggesting that the nucleocytoplasmic shuttling of proteins is a mechanism in nuclear signaling. We seek to understand how synapses relay fast synaptic information to the nucleus and specifically what are the key players in this process, what signals they respond to and what are their nuclear functions. To study this, we use proteomics and mass spectrometry to explore the composition and dynamics of excitatory synapses and nuclei. These methods provide us with a global view of synaptic complexity as well as help us identify novel components of synapse-to-nucleus signaling mechanisms, which we can then further study using reductionist methods in cell and molecular biology as well as biochemistry and imaging analysis. Using these methods we found that a number of synaptic components can shuttle to the nucleus in response to synaptic activity. We also found that a number of nuclear proteins are incorporated into the synapse in response to synaptic activity suggesting that the reverse pathway, nucleus-to-signaling pathway also affects synaptic transmission. Our immediate goal is to study these novel synapse to nucleus signaling messengers and to explore their synaptic and nuclear functions.

Selected Publications

Jacob AL, Jordan BA, Weinberg RJ. (2010) Organization of amyloid-beta protein precursor intracellular domain-associated protein-1 in the rat brain.  J Comp Neurol. Aug 15;518(16):3221-36.

Jordan BA, Kreutz MR. (2009) Nucleocytoplasmic protein shuttling: the direct route in synapse-to-nucleus signaling. Trends in Neurosci (TINS).  Jul;32(7):392-401.

Jordan BA., Fernholz BD., Khatri L., Ziff EB. NMDA receptor-dependent AIDA-1 synapse-to-nucleus signaling regulates nucleolar number in neurons. Nat. Neurosci. (2007) Apr; 10(4):427-35.

Jordan BA, Ziff EB.  To the Nucleus with Proteomics. In Regulation of Transcription by Neuronal Activity. Edited by: Dudek SM. Springer Science; November 2007.

Jordan BA., Ziff EB. (2006) Getting to synaptic complexes through systems biology.  Genome Biology 7:214. doi:10.1186/gb-2006-7-4-214.

Monea, S., Jordan BA., Srivastava S., DeSouza S., and Ziff EB. (2006) Membrane Localization of Membrane Type 5 Matrix Metalloproteinase by AMPA Receptor Binding Protein and Cleavage of Cadherins. J. Neurosci. 26: 2300-2312.

Jordan BA, Fernholz BD, Neubert TA, Ziff EB. (2006)  New tricks for an old dog: proteomics of the PSD. In The Dynamic Synapse: Molecular Methods in Ionotropic Receptor Biology. Volume 29. Edited by: Kittler JT, Moss SJ. Boca Raton: CRC/Taylor & Francis:37-55.

Jordan, BA., Fernholz, BD., Boussac, M., Xu, C., Grigorean, G., Ziff, EB., and Neubert, TA. (2004) Identification and Verification of Novel Rodent Postsynaptic Density Proteins. Mol. Cell. Proteomics 3(9):857-71

Jordan BA, Gomes I, Rios CD, Filipovska J, Devi L. (2003)  mu opioid and a2a-adrenergic receptor interactions in neurons.  Mol Pharm 64(6) 1317-1324

Gomes I, Filipovska J, Jordan BA, Devi LA. (2002)  Oligomerization of opioid receptors. Methods 27 (4): 358-365.

Rios CD, Jordan BA, Gomes I, and Devi LA. (2001) G-protein-coupled receptor dimerization: modulation of receptor function. Pharmacol Therapeut 92 (2-3): 71-87.

Gomes I, Jordan BA, Gupta A, Rios C, Trapaidze N, Devi LA. (2001) G protein coupled receptor dimerization: implications in modulating receptor function. Journal of Mol Med 79 (5-6): 226-242.

Jordan, BA., Trapaidze, N., Gomes, I., Nivarthi, R., and Devi, L. (2001) Opioid receptors heterodimerize with beta-adrenergic receptors: A role in trafficking and MAPK activation. PNAS 98(1): 343-348.

Gomes, I., Jordan, BA., Nagy, V., Trapaidze, N., Bansinath, M. and Devi, L. (2000) Interaction between Mu and Delta opioid receptors: A role for dimerization in opioid receptor cross-talk. J. Neurosci. 20: RC110.

Jordan, BA., Cvejic, S., and Devi, L. (2000) Opioids and their complicated receptor complexes,  Neuropsychopharmacology.  19, 19-27.

Jordan, BA., Cvejic, S. and Devi, L. (2000) Kappa opioid receptor endocytosis by dynorphin peptides, DNA Cell Biol. 19, 19-27.

Jordan, BA. and Devi, L. (1999) G protein coupled receptor heterodimerization modulates receptor function. Nature 399, 697-700.

Jordan, B. and Devi, L. (1998) Molecular mechanisms of opioid receptor signal transduction. Br J Anaesta 81;12-19.