Description:

The Departments of Physiology and Pharmacology invite faculty, staff, and students to a mini-symposium with refreshments –“Synaptic Structure and Function.”

Friday, October 16, 2015
Physiology Conference Room – Ward 5-230, 303 E. Chicago Avenue

12:00pm -- “The C1q Complement Family: Unique Functional and Morphological Regulators of Synapses in the CNS” with Michisuke Yuzaki, MD, PhD, Professor and Chair of the Department of Physiology, Keio University School of Medicine.

12:45pm -- “Molecular Mechanism of Hippocampal Synaptic Plasticity” with Yasunori Hayashi, MD, PhD, Senior Team Leader with the Brain Science Institute at RIKEN.

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“The C1q Complement Family: Unique Functional and Morphological Regulators of Synapses in the CNS”

Presentation Abstract: C1q is the target recognition protein of the complement pathway in the innate immune response. C1q family proteins are mostly secreted and involved in various intracellular signaling and extracellular matrix formation. We have shown previously that a C1q family protein Cbln1 is secreted from cerebellar granule cells and binds to its presynaptic receptor neurexin located on granule cell axons and its postsynaptic receptor the delta2 glutamate receptor (GluD2) on dendritic spines of Purkinje cells (Matsuda e al, Science 2010). The neurexin/Cbln1/GluD2 tripartite complex is essential for formation of presynaptic boutons (Ito-Ishida et al, Neuron 2012). In addition, we have recently shown that C1q-like 1 (C1qL1), another C1q family member, is secreted from climbing fibers (CFs) and serves as a crucial anterograde signal to determine and maintain the single-winner CF in the mouse cerebellum throughout development and adulthood (Kakegawa, Neuron 2015). C1qL1 specifically binds to the brain-specific angiogenesis inhibitor 3 (Bai3), a member of the cell-adhesion G-protein-coupled receptors, expressed on postsynaptic Purkinje cells. Because related family members of Cbln1 and C1qL1 are expressed in various brain regions, C1q family proteins likely mediate synapse formation, maintenance, and function in multiple neuronal circuits essential for important brain functions.

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“Molecular Mechanism of Hippocampal Synaptic Plasticity”

Presentation Abstract: Upon long-term potentiation2+ influx through NMDAR is converted into a long-lasting increase in synaptic transmission and an enlargement of the dendritic spines. There must be a point within the signaling cascade where transient Ca2+ raise is converted to a persistent biochemical signaling. Here, we identified a formation of a stable heterooligomer between CaMKII and TIAM1, a Rac specific guanine-nucleotide exchange factor, as the point of the conversion. The binding of TIAM1 on “T-site” of CaMKII locks CaMKII in an active conformation mimicking the action of T286 autophosphorylation, which, in turn, results in a persistent activation of TIAM1 by phosphorylation. This mutually activating complex persistently activate of Rac, which is required for the maintenance of LTP. We conclude, CaMKII acts as a signaling hub that, once activated by Ca2+, can persistently activating TIAM1 and possibly other signaling molecules at the vicinity of active synapse.

Refreshments will be served.

Please e-mail Donna Daviston at d-daviston@northwestern.edu or Alexa Nash at alexa.nash@northwestern.edu if you have any questions.