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Notes for 12/1/03 discussion

Notes for 12/1/03 discussion. Papers: Zhou, Q. et al ., (2003) “Reversal and Stabilization of Synaptic Modifications in a Developing Visual System” Science 300 :1953-1957 Quattrocchi, C. et al ., (2003) “Reelin Promotes Peripheral Synapse Elimination and Maturation” Science 301 :649-653.

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Notes for 12/1/03 discussion

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  1. Notes for 12/1/03 discussion Papers: Zhou, Q. et al., (2003) “Reversal and Stabilization of Synaptic Modifications in a Developing Visual System” Science 300:1953-1957 Quattrocchi, C. et al., (2003) “Reelin Promotes Peripheral Synapse Elimination and Maturation” Science 301:649-653

  2. Zhou, Q. et al. Supplemental Material: http://www.sciencemag.org/cgi/data/300/5627/1953/DC1/1 Quick Electrophysiology Reminders: Voltage Clamp: neuron is held at particular voltage by current injection, and the current required to maintain that voltage is recorded Current Clamp: current injection is held constant, for example, at 0 mA

  3. Kynurenic Acid Kynurenic acid is an “antagonist at NMDA, kainate and AMPA receptors [5]. Kynurenic acid can block glutamate receptors in rodents [5] and primates [6] and can distinguish subpopulations of kainate receptors [7]. In addition, there is evidence for an additional, novel site of action of kynurenic acid [2]. Several years after the realization that kynurenic acid was an antagonist at all subtypes of glutamate receptor [5] it was found to be particularly active as an antagonist at an allosteric site on the NMDA receptor [8] for which glycine or   -serine might be endogenous, essential co-agonists.” Fig. 1. The major components of the kynurenine pathway that possess neurobiological activity are shown. The pathway, which accounts for the majority of non-protein tryptophan metabolism in most tissues, includes quinolinic acid (an agonist at NMDA receptors[2 and 3]), 3-hydroxykynurenine (a radical-generating neurotoxin [9]) and kynurenic acid (a glutamate receptor antagonist with differences in potency at the various receptor subtypes [2 and 5]). http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T1K-40199B0-C&_coverDate=04%2F01%2F2000&_alid=131238353&_rdoc=1&_fmt=&_orig=search&_qd=1&_cdi=4893&_sort=d&view=c&_acct=C000020998&_version=1&_urlVersion=0&_userid=441497&md5=0e87906bae1e3a2fac66d104e31ee686#toc1

  4. Quattrocchi, C. et al. Supplemental information: http://www.sciencemag.org/cgi/data/301/5633/649/DC1/1 Serine Proteases: Proteases, proteinases or peptidases describe the same group of enzymes that catalyse the hydrolysis of covalent peptidic bonds. In the case of serine proteases the mechanism (from Mellon College of Science Courses) is based on nucleophilic attack of the targeted peptidic bond by a serine URL for mechanism: http://www.bio.cmu.edu/courses/03231/Protease/SerPro.htm (http://biochem.wustl.edu/~protease/ser_pro_overview.html) Inhibitors: Pefabloc SC: Irreversibly inhibits serine proteases, including trypsin, chymotrypsin, plasmin, plasma kallikrein, and thrombin. Suggested starting concentration: 0.1–1.0 mg / ml (0.4–4 mM) Leupeptin: Inhibits serine and cysteine proteases such as trypsin, papain, plasmin, and cathepsin B. Suggested starting concentration: 0.5 µg / ml (1 µM) (http://www.roche-applied-science.com/fst/products.htm?/proteaseinhibitor/)

  5. Reelin Signaling Figure 5 | Reelin signaling.   Binding of reelin to very-low-density lipoprotein receptor (Vldlr) or ApoE receptor 2 (ApoER2) results in tyrosine phosphorylation of Dab1, the mouse homologue of Disabled, which interacts with the cytoplasmic tail of either receptor. Tyrosine phosphorylation of Dab1 is necessary for the activation of downstream signalling cascades that ultimately mediate the cellular effects of reelin. The identity of the kinases that tyrosine phosphorylate Dab1 has not been established, although non-receptor tyrosine kinases of the Src family are potential candidates. Consistent with this theory, Fyn and Src bind to cadherin-related neuronal receptors (Cnrs) and integrins, respectively, which are also receptors for Reln.

  6. Miscellaneous Notes: Soleus: slow-twitch muscle of the hindlimb (“ankle” region) a-bungarotoxin: binds nicotinic acetylcholine receptor, TRITC is a fluorescent tag Neurofilament 200: “Neurofilaments are major constituents of the axonal cytoskeleton. Like most other intermediate filament proteins (IFPs), the expression of the different neuronal IFPs is both tissue-specific and developmentally regulated. The 200 kDa neurofilament protein is abundantly expressed in the spinal cord, cerebellum, pons and medulla. These are predominantly brain regions giving rise to long-axon neurons.” (http://www.bioreagents.com/index.cfm/fuseaction/products.detail/CatNbr/OMA1-06115) Reelin was shown to be a serine protease of the extracellular matrix and to degrade fibronectin in a previous Quattrocchi publication. Quattrocchi et al. (2002) Journal of Biological Chemistry 277:303-309 (http://www.jbc.org/cgi/reprint/277/1/303)

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