Abstract
The effects of nerve growth factor (NGF) on the expression of neural cell adhesion molecule (N-CAM) in PC12 cells were determined. A quantitative immunoassay was used to show that NGF induces a 4- to 5-fold increase in relative N-CAM levels over a 3-day period. This increase could not be mimicked by cholera toxin suggesting that it is not a simple consequence of morphological differentiation. The changes in N-CAM levels induced by NGF were accompanied by changes in N-CAM molecular forms. The 140-kd N-CAM species is the major N-CAM expressed by naive PC12 cells, while NGF-treated cultures express N-CAM species of 180 kd and 140 kd. Northern analysis showed that naive cells express a 6.7-kd N-CAM mRNA species only, while NGF-treated cultures express both a 6.7-kb and a 7.2-kb transcript. As the 6.7-kb and 7.2-kb mRNAs are alternative spliced transcripts of a single gene, this result shows that NGF can activate a neuron-specific splicing mechanism. This is the first description of control of N-CAM expression by a growth factor.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bock E., Richter-Landsberg C., Faissner A., Schachner M. Demonstration of immunochemical identity between the nerve growth factor-inducible large external (NILE) glycoprotein and the cell adhesion molecule L1. EMBO J. 1985 Nov;4(11):2765–2768. doi: 10.1002/j.1460-2075.1985.tb04001.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Burstein D. E., Greene L. A. Evidence for RNA synthesis-dependent and -independent pathways in stimulation of neurite outgrowth by nerve growth factor. Proc Natl Acad Sci U S A. 1978 Dec;75(12):6059–6063. doi: 10.1073/pnas.75.12.6059. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Caplan A. I., Fiszman M. Y., Eppenberger H. M. Molecular and cell isoforms during development. Science. 1983 Sep 2;221(4614):921–927. doi: 10.1126/science.6348946. [DOI] [PubMed] [Google Scholar]
- Covault J., Merlie J. P., Goridis C., Sanes J. R. Molecular forms of N-CAM and its RNA in developing and denervated skeletal muscle. J Cell Biol. 1986 Mar;102(3):731–739. doi: 10.1083/jcb.102.3.731. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cunningham B. A., Hoffman S., Rutishauser U., Hemperly J. J., Edelman G. M. Molecular topography of the neural cell adhesion molecule N-CAM: surface orientation and location of sialic acid-rich and binding regions. Proc Natl Acad Sci U S A. 1983 May;80(10):3116–3120. doi: 10.1073/pnas.80.10.3116. [DOI] [PMC free article] [PubMed] [Google Scholar]
- D'Eustachio P., Owens G. C., Edelman G. M., Cunningham B. A. Chromosomal location of the gene encoding the neural cell adhesion molecule (N-CAM) in the mouse. Proc Natl Acad Sci U S A. 1985 Nov;82(22):7631–7635. doi: 10.1073/pnas.82.22.7631. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dickson G., Prentice H., Julien J. P., Ferrari G., Leon A., Walsh F. S. Nerve growth factor activates Thy-1 and neurofilament gene transcription in rat PC12 cells. EMBO J. 1986 Dec 20;5(13):3449–3453. doi: 10.1002/j.1460-2075.1986.tb04668.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dickson J. G., Prentice H. M., Kenimer J. G., Walsh F. S. Identification and characterization of neuron-specific and developmentally regulated gene transcripts in the chick embryo spinal cord. J Neurochem. 1986 Mar;46(3):787–793. doi: 10.1111/j.1471-4159.1986.tb13041.x. [DOI] [PubMed] [Google Scholar]
- Edelman G. M. Cell adhesion and the molecular processes of morphogenesis. Annu Rev Biochem. 1985;54:135–169. doi: 10.1146/annurev.bi.54.070185.001031. [DOI] [PubMed] [Google Scholar]
- Edelman G. M. Modulation of cell adhesion during induction, histogenesis, and perinatal development of the nervous system. Annu Rev Neurosci. 1984;7:339–377. doi: 10.1146/annurev.ne.07.030184.002011. [DOI] [PubMed] [Google Scholar]
- Friedlander D. R., Grumet M., Edelman G. M. Nerve growth factor enhances expression of neuron-glia cell adhesion molecule in PC12 cells. J Cell Biol. 1986 Feb;102(2):413–419. doi: 10.1083/jcb.102.2.413. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gennarini G., Hirsch M. R., He H. T., Hirn M., Finne J., Goridis C. Differential expression of mouse neural cell-adhesion molecule (N-CAM) mRNA species during brain development and in neural cell lines. J Neurosci. 1986 Jul;6(7):1983–1990. doi: 10.1523/JNEUROSCI.06-07-01983.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goridis C., Hirn M., Santoni M. J., Gennarini G., Deagostini-Bazin H., Jordan B. R., Kiefer M., Steinmetz M. Isolation of mouse N-CAM-related cDNA: detection and cloning using monoclonal antibodies. EMBO J. 1985 Mar;4(3):631–635. doi: 10.1002/j.1460-2075.1985.tb03676.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Greene L. A., Burstein D. E., Black M. M. The role of transcription-dependent priming in nerve growth factor promoted neurite outgrowth. Dev Biol. 1982 Jun;91(2):305–316. doi: 10.1016/0012-1606(82)90037-9. [DOI] [PubMed] [Google Scholar]
- Greene L. A., Tischler A. S. Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor. Proc Natl Acad Sci U S A. 1976 Jul;73(7):2424–2428. doi: 10.1073/pnas.73.7.2424. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gunning P. W., Landreth G. E., Layer P., Ignatius M., Shooter E. M. Nerve growth factor-induced differentiation of PC12 cells: evaluation of changes in RNA and DNA metabolism. J Neurosci. 1981 Apr;1(4):368–379. doi: 10.1523/JNEUROSCI.01-04-00368.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moore S. E., Walsh F. S. Specific regulation of N-CAM/D2-CAM cell adhesion molecule during skeletal muscle development. EMBO J. 1985 Mar;4(3):623–630. doi: 10.1002/j.1460-2075.1985.tb03675.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Murray B. A., Hemperly J. J., Gallin W. J., MacGregor J. S., Edelman G. M., Cunningham B. A. Isolation of cDNA clones for the chicken neural cell adhesion molecule (N-CAM). Proc Natl Acad Sci U S A. 1984 Sep;81(17):5584–5588. doi: 10.1073/pnas.81.17.5584. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Murray B. A., Hemperly J. J., Prediger E. A., Edelman G. M., Cunningham B. A. Alternatively spliced mRNAs code for different polypeptide chains of the chicken neural cell adhesion molecule (N-CAM). J Cell Biol. 1986 Jan;102(1):189–193. doi: 10.1083/jcb.102.1.189. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Murray B. A., Owens G. C., Prediger E. A., Crossin K. L., Cunningham B. A., Edelman G. M. Cell surface modulation of the neural cell adhesion molecule resulting from alternative mRNA splicing in a tissue-specific developmental sequence. J Cell Biol. 1986 Oct;103(4):1431–1439. doi: 10.1083/jcb.103.4.1431. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nguyen C., Mattei M. G., Mattei J. F., Santoni M. J., Goridis C., Jordan B. R. Localization of the human NCAM gene to band q23 of chromosome 11: the third gene coding for a cell interaction molecule mapped to the distal portion of the long arm of chromosome 11. J Cell Biol. 1986 Mar;102(3):711–715. doi: 10.1083/jcb.102.3.711. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pollerberg E. G., Sadoul R., Goridis C., Schachner M. Selective expression of the 180-kD component of the neural cell adhesion molecule N-CAM during development. J Cell Biol. 1985 Nov;101(5 Pt 1):1921–1929. doi: 10.1083/jcb.101.5.1921. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pollerberg G. E., Schachner M., Davoust J. Differentiation state-dependent surface mobilities of two forms of the neural cell adhesion molecule. Nature. 1986 Dec 4;324(6096):462–465. doi: 10.1038/324462a0. [DOI] [PubMed] [Google Scholar]
- Richter-Landsberg C., Greene L. A., Shelanski M. L. Cell surface Thy-1-cross-reactive glycoprotein in cultured PC12 cells: modulation by nerve growth factor and association with the cytoskeleton. J Neurosci. 1985 Feb;5(2):468–476. doi: 10.1523/JNEUROSCI.05-02-00468.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Richter-Landsberg C., Jastorff B. The role of cAMP in nerve growth factor-promoted neurite outgrowth in PC12 cells. J Cell Biol. 1986 Mar;102(3):821–829. doi: 10.1083/jcb.102.3.821. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rutishauser U. Developmental biology of a neural cell adhesion molecule. Nature. 1984 Aug 16;310(5978):549–554. doi: 10.1038/310549a0. [DOI] [PubMed] [Google Scholar]
- Salton S. R., Richter-Landsberg C., Greene L. A., Shelanski M. L. Nerve growth factor-inducible large external (NILE) glycoprotein: studies of a central and peripheral neuronal marker. J Neurosci. 1983 Mar;3(3):441–454. doi: 10.1523/JNEUROSCI.03-03-00441.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Walsh F. S., Phillips E., Dhut S., Moore S. E. Extracellular matrix antigen of human muscle defined by a monoclonal antibody. J Neuroimmunol. 1983 Aug;5(1):11–31. doi: 10.1016/0165-5728(83)90023-1. [DOI] [PubMed] [Google Scholar]
- Walsh F. S., Putt W., Dickson J. G., Quinn C. A., Cox R. D., Webb M., Spurr N., Goodfellow P. N. Human N-CAM gene: mapping to chromosome 11 by analysis of somatic cell hybrids with mouse and human cDNA probes. Brain Res. 1986 Nov;387(2):197–200. doi: 10.1016/0169-328x(86)90012-4. [DOI] [PubMed] [Google Scholar]