The work in this proposal addresses two issues of fundamental importance to our understanding of neuronal function and development. The first is to determine how membrane glycoproteins synthesized in the cell body of a neuron are selectively routed to the pre- and postsynaptic terminal. These processes are central to the proper assembly of surface membranes and to how distinct regions of the neuronal plasma membrane are maintained in a functionally and structurally differentiated state. The second concerns the possible role of glycoproteins as mediators of interneuronal recognition and adhesion. My colleagues and I intend to explore these points using a single cell - R2 the giant neuron of Aplysia californica. R2's cell body, presynaptic, and postsynaptic regions are anatomically accessible. Moreover, R2 synthesizes only ten membrane glycoproteins, a remarkable simplicity relative to the complexity of glycoprotein fractions from vertebrate nervous tissue. Two of R2's glycoproteins have distinctly different destinations in the cell: glycoprotein-I is the major glycoprotein on the cell surface of the cell soma whereas glycoprotein-V is preferentially exported into the axon where it is rapidly transported towards R2's synapses. The site at which the two glycoproteins are sorted will be determined by immunocytochemistry at the ultrastructural level using monoclonal antibodies raised to each glycoprotein. In addition, the oligosaccharide chains of both glycoproteins will be characterized with the idea that a modification of a glycosyl moiety is the signal responsible for the sorting. R2, GCN, and R15 are three large identified neurons that differ in function, location, and neurotransmitter type. We will examine the glycoproteins present on the surface of the cell body and terminals of these neurons in order to test directly the hypothesis that neurons can be distinguished by their glycoprotein constituents. Many features of the proposed experiments are unique and present a unified, multidisciplinary approach to issues of major importance to our knowledge of the neuron.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS022150-01
Application #
3404190
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1985-04-01
Project End
1988-03-31
Budget Start
1985-04-01
Budget End
1986-03-31
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Type
Schools of Medicine
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10027
Sung, Y J; Chiu, D T W; Ambron, R T (2006) Activation and retrograde transport of protein kinase G in rat nociceptive neurons after nerve injury and inflammation. Neuroscience 141:697-709
Sung, Ying-Ju; Wu, Fang; Schacher, Samuel et al. (2006) Synaptogenesis regulates axotomy-induced activation of c-Jun-activator protein-1 transcription. J Neurosci 26:6439-49
Colby, Geoffrey P; Sung, Ying-Ju; Ambron, Richard T (2005) mRNAs encoding the Aplysia homologues of fasciclin-I and beta-thymosin are expressed only in the second phase of nerve injury and are differentially segregated in axons regenerating in vitro and in vivo. J Neurosci Res 82:484-98
Sung, Ying-Ju; Ambron, Richard T (2004) Pathways that elicit long-term changes in gene expression in nociceptive neurons following nerve injury: contributions to neuropathic pain. Neurol Res 26:195-203
Sung, Ying-Ju; Walters, Edgar T; Ambron, Richard T (2004) A neuronal isoform of protein kinase G couples mitogen-activated protein kinase nuclear import to axotomy-induced long-term hyperexcitability in Aplysia sensory neurons. J Neurosci 24:7583-95
Lin, Hana; Bao, Jianxin; Sung, Ying-Ju et al. (2003) Rapid electrical and delayed molecular signals regulate the serum response element after nerve injury: convergence of injury and learning signals. J Neurobiol 57:204-20
Farr, M; Zhu, D F; Povelones, M et al. (2001) Direct interactions between immunocytes and neurons after axotomy in Aplysia. J Neurobiol 46:89-96
Sung, Y J; Povelones, M; Ambron, R T (2001) RISK-1: a novel MAPK homologue in axoplasm that is activated and retrogradely transported after nerve injury. J Neurobiol 47:67-79
Zhang, X P; Ambron, R T (2000) Positive injury signals induce growth and prolong survival in Aplysia neurons. J Neurobiol 45:84-94
Farr, M; Mathews, J; Zhu, D F et al. (1999) Inflammation causes a long-term hyperexcitability in the nociceptive sensory neurons of Aplysia. Learn Mem 6:331-40

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