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The Marshall W. Nirenberg Papers

Laboratory project: "Cell Recognition and Synapse Formation" pdf (222,616 Bytes) transcript of pdf
Laboratory project: "Cell Recognition and Synapse Formation"
Summary of work for this project as indicated on the report: "Long range objectives are to define reactions which are required for synapse formation and for transmission of information from cell to cell."
Item is a photocopy.
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3 (222,616 Bytes)
1976-09 (September 1976)
Nirenberg, Marshall W.
Puro, Donald
Sugiyama, Hiroyuki
Nelson, Phillip
Christian, Clifford
National Heart and Lung Institute. Laboratory of Biochemical Genetics
This item is in the public domain. It may be used without permission.
Exhibit Categories:
From Neuroblastoma to Homeobox Genes, 1976-1992
Neuroblastoma Research, 1967-1976
Metadata Record Annual Report of the Laboratory of Biochemical Genetics, October 1, 1975 - September 30, 1976 (September 1976)
Box Number:
31 of 31
Unique Identifier:
Accession Number:
Document Type:
Physical Condition:
Project Number: Z01 HL 00009-02 LBG
Period Covered: July 1, 1975 through June 30, 1976
Title of Project: Cell Recognition and Synapse Formation
Names, Laboratory and Institute Affiliations, and Titles of Principal Investigators and All Other Professional Personnel Engaged on the Project:
PI: Marshall Nirenberg, Chief, Lab. of Biochemical Genetics, LBG NHLI
OTHER: Donald Puro, Research Associate, LBG NHLI
Hiroyuki Sugiyama, Visiting Associate, LBG NHLI
Phillip Nelson, Chief, Behavioral Biology Branch, BB NICHD
Clifford Christian, Special Fellow, BB NICHD
Cooperating Units (if any): Behavioral Biology Branch, NICHD
Lab/Branch: Laboratory of Biochemical Genetics
Section: Section on Molecular Biology
Institute and Location: NHLI, NIH, Bethesda, MD 20014
Total Man Years: 2.2
Professional: 2
Other: .2
Summary of Work: Long range objectives are to define reactions which are required for synapse formation and for transmission of information from cell to cell.
Project Description:
Major Findings: Since normal neurons do not divide, clonal lines of neuroblastoma cells and somatic cell hybrids derived from neuroblastoma cells were generated and characterized with respect to receptors, neurotransmitters, action potential ionophores, and other properties which are required for synaptic communication. Fusion of clonal neuroblastoma cells with glioma cells yielded clonal hybrid cell lines which synthesize, store and excrete acetylcholine; properties which are not expressed by the parental cell lines. During the past year cells from one hybrid line were found to form synapses with cultured striated muscle cells. Synapses between hybrid cells and muscle cells closely resemble the synapses between normal motor neurons and striated muscle before they are fully developed. Under appropriate conditions, hybrid cells established synaptic connections with almost every muscle cell tested; thus, synapses are synthesized in abundance. Marked differences were observed in the efficiency of transmission across different synapses. Axonal activities which were found to be regulated include choline acetyltransferase, acetylcholinesterase, Na+ action potential ionophore specific activities, and the rate of choline transport into cells.
Eight species of receptors have been found thus far with the hybrid cell line which forms synapses. Receptor mediated shifts in cAMP levels, cGMP levels and membrane potentials have been identified and characterized. Thus the foundation has been laid for studies on the effects of receptor-mediated reactions on synaptic transmission. In addition, more than 100 cell lines which synthesize acetylcholine have been obtained and are being studied to determine that some cell lines are defective with respect to synapse formation.
Significance to Biomedical Research: This is the first time that clonal cells of neural origin have been shown to form synapses. Thus the set of genes which are required for synapse formation are expressed in this cell line. The model system which has been established affords extraordinary opportunities to define synapse formation reactions and properties and correlate biochemical events with developmental and electrophysiological phenomena.
Proposed Course: Current studies focus on determining the reactions which are required for synapse formation and factors that regulate these reactions.
1. Greene, Lloyd A., Shain, William, Chalazonitis, Alcmene, Breakefield, Xandra, Minna, John, Coon, Hayden G. and Nirenberg, Marshall: Neuronal properties of hybrid neuroblastoma x sympathetic ganglion cells. Proc. Natl. Acad. Sci. USA 72: 4923-4927, 1975.
2. Chalazonitis, A., Greene, L.A. and Shain W.: Excitability and chemosensitivity properties of a somatic cell hybrid between mouse neuroblastoma and sympathetic ganglion cells. Exp. Cell Res. 96: 225-238, 1975.
3. Nelson, Phillip, Christian, Clifford and Nirenberg, Marshall: Synapse formation between clonal neuroblastoma x glioma hybrid cells and striated muscle cells. Proc. Natl. Acad. Sci. USA 73: 123-127, 1976.
4. Nirenberg, Marshall W.: Coding of neural information by neuroblastoma cells. In: Talwar, G. P. (Ed.): Regulation of Growth and Differentiated Function in Eukaryote Cells. New York, Raven Press, pp. 537-539, 1975
5. Thompson, Edward J., Griffith, James M., Glazer-Schoenberg, Deverera and Nirenberg, Marshall W.: An improved method for extracellular recording of action potentials from single cultured neuroblastoma cells. Med. Biol. Eng. 13: 104-106, 1975.
6. Hamprecht, Bernd, Kemper, Wayne and Amano, Takehiko: Electrical response of glioma cells to acetylcholine. Brain Res. 101: 129-135, 1976.
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