Abstract
The rodent neural cell adhesion molecule (NCAM) consists of three glycoproteins with Mr of 180,000, 140,000 and 120,000. The Mr 120,000 protein (NCAM-120) has been shown to exist in membrane-bound and soluble forms but the nature of its membrane association and release has remained obscure. We show here that phosphatidylinositol-specific phospholipase C (PI-PLC), but not a phospholipase C of different specificity, releases a substantial proportion of NCAM-120 from brain membranes and solubilizes almost quantitatively NCAM-120 present at the surface of C6 astroglial cells. The PI-PLC effect was highly selective since only one other protein species was detectably released from C6 cells. These results suggest that NCAM-120 is held in the membrane by covalently bound phosphatidylinositol or a closely related lipid in a way similar to several other surface proteins from eukaryotic cells. The presence of NCAM in a form which can be released from the cell surface by a highly selective mechanism raises additional possibilities for modulation and control of cell--cell adhesion.
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- Benda P., Lightbody J., Sato G., Levine L., Sweet W. Differentiated rat glial cell strain in tissue culture. Science. 1968 Jul 26;161(3839):370–371. doi: 10.1126/science.161.3839.370. [DOI] [PubMed] [Google Scholar]
- Berridge M. J. Inositol trisphosphate and diacylglycerol as second messengers. Biochem J. 1984 Jun 1;220(2):345–360. doi: 10.1042/bj2200345. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Chuong C. M., Edelman G. M. Alterations in neural cell adhesion molecules during development of different regions of the nervous system. J Neurosci. 1984 Sep;4(9):2354–2368. doi: 10.1523/JNEUROSCI.04-09-02354.1984. [DOI] [PMC free article] [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]
- Culp L. A. Substrate-attached glycoproteins mediating adhesion of normal and virus-transformed mouse fibroblasts. J Cell Biol. 1974 Oct;63(1):71–83. doi: 10.1083/jcb.63.1.71. [DOI] [PMC free article] [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]
- Ferguson M. A., Low M. G., Cross G. A. Glycosyl-sn-1,2-dimyristylphosphatidylinositol is covalently linked to Trypanosoma brucei variant surface glycoprotein. J Biol Chem. 1985 Nov 25;260(27):14547–14555. [PubMed] [Google Scholar]
- Futerman A. H., Low M. G., Silman I. A hydrophobic dimer of acetylcholinesterase from Torpedo californica electric organ is solubilized by phosphatidylinositol-specific phospholipase C. Neurosci Lett. 1983 Sep 19;40(1):85–89. doi: 10.1016/0304-3940(83)90097-6. [DOI] [PubMed] [Google Scholar]
- Gennarini G., Hirn M., Deagostini-Bazin H., Goridis C. Studies on the transmembrane disposition of the neural cell adhesion molecule N-CAM. The use of liposome-inserted radioiodinated N-CAM to study its transbilayer orientation. Eur J Biochem. 1984 Jul 2;142(1):65–73. doi: 10.1111/j.1432-1033.1984.tb08251.x. [DOI] [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]
- Gennarini G., Rougon G., Deagostini-Bazin H., Hirn M., Goridis C. Studies on the transmembrane disposition of the neural cell adhesion molecule N-CAM. A monoclonal antibody recognizing a cytoplasmic domain and evidence for the presence of phosphoserine residues. Eur J Biochem. 1984 Jul 2;142(1):57–64. doi: 10.1111/j.1432-1033.1984.tb08250.x. [DOI] [PubMed] [Google Scholar]
- Hansen O. C., Nybroe O., Bock E. Cell-free synthesis of the D2-cell adhesion molecule: evidence for three primary translation products. J Neurochem. 1985 Mar;44(3):712–717. doi: 10.1111/j.1471-4159.1985.tb12873.x. [DOI] [PubMed] [Google Scholar]
- Hausman R. E., Moscona A. A. Purification and characterization of the retina-specific cell-aggregating factor. Proc Natl Acad Sci U S A. 1975 Mar;72(3):916–920. doi: 10.1073/pnas.72.3.916. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hirn M., Ghandour M. S., Deagostini-Bazin H., Goridis C. Molecular heterogeneity and structural evolution during cerebellar ontogeny detected by monoclonal antibody of the mouse cell surface antigen BSP-2. Brain Res. 1983 Apr 11;265(1):87–100. doi: 10.1016/0006-8993(83)91337-9. [DOI] [PubMed] [Google Scholar]
- Hoffman S., Edelman G. M. Kinetics of homophilic binding by embryonic and adult forms of the neural cell adhesion molecule. Proc Natl Acad Sci U S A. 1983 Sep;80(18):5762–5766. doi: 10.1073/pnas.80.18.5762. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Keilhauer G., Faissner A., Schachner M. Differential inhibition of neurone-neurone, neurone-astrocyte and astrocyte-astrocyte adhesion by L1, L2 and N-CAM antibodies. Nature. 1985 Aug 22;316(6030):728–730. doi: 10.1038/316728a0. [DOI] [PubMed] [Google Scholar]
- Low M. G., Finean J. B. Specific release of plasma membrane enzymes by a phosphatidylinositol-specific phospholipase C. Biochim Biophys Acta. 1978 Apr 20;508(3):565–570. doi: 10.1016/0005-2736(78)90100-1. [DOI] [PubMed] [Google Scholar]
- Low M. G., Kincade P. W. Phosphatidylinositol is the membrane-anchoring domain of the Thy-1 glycoprotein. Nature. 1985 Nov 7;318(6041):62–64. doi: 10.1038/318062a0. [DOI] [PubMed] [Google Scholar]
- Low M. G. Phosphatidylinositol-specific phospholipase C from Staphylococcus aureus. Methods Enzymol. 1981;71(Pt 100):741–746. doi: 10.1016/0076-6879(81)71087-5. [DOI] [PubMed] [Google Scholar]
- Low M. G., Zilversmit D. B. Role of phosphatidylinositol in attachment of alkaline phosphatase to membranes. Biochemistry. 1980 Aug 19;19(17):3913–3918. doi: 10.1021/bi00558a004. [DOI] [PubMed] [Google Scholar]
- Michell R. H. Inositol phospholipids and cell surface receptor function. Biochim Biophys Acta. 1975 Mar 25;415(1):81–47. doi: 10.1016/0304-4157(75)90017-9. [DOI] [PubMed] [Google Scholar]
- Noble M., Albrechtsen M., Møller C., Lyles J., Bock E., Goridis C., Watanabe M., Rutishauser U. Glial cells express N-CAM/D2-CAM-like polypeptides in vitro. Nature. 1985 Aug 22;316(6030):725–728. doi: 10.1038/316725a0. [DOI] [PubMed] [Google Scholar]
- Nybroe O., Albrechtsen M., Dahlin J., Linnemann D., Lyles J. M., Møller C. J., Bock E. Biosynthesis of the neural cell adhesion molecule: characterization of polypeptide C. J Cell Biol. 1985 Dec;101(6):2310–2315. doi: 10.1083/jcb.101.6.2310. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rothbard J. B., Brackenbury R., Cunningham B. A., Edelman G. M. Differences in the carbohydrate structures of neural cell-adhesion molecules from adult and embryonic chicken brains. J Biol Chem. 1982 Sep 25;257(18):11064–11069. [PubMed] [Google Scholar]
- Rougon G., Deagostini-Bazin H., Hirn M., Goridis C. Tissue- and developmental stage-specific forms of a neural cell surface antigen linked to differences in glycosylation of a common polypeptide. EMBO J. 1982;1(10):1239–1244. doi: 10.1002/j.1460-2075.1982.tb00019.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rougon G., Marshak D. R. Structural and immunological characterization of the amino-terminal domain of mammalian neural cell adhesion molecules. J Biol Chem. 1986 Mar 5;261(7):3396–3401. [PubMed] [Google Scholar]
- Sadoul R., Hirn M., Deagostini-Bazin H., Rougon G., Goridis C. Adult and embryonic mouse neural cell adhesion molecules have different binding properties. 1983 Jul 28-Aug 3Nature. 304(5924):347–349. doi: 10.1038/304347a0. [DOI] [PubMed] [Google Scholar]
- Spiegel J., Garber B. Sorting out of coaggregated brain cell types mediated by specific cell recognition factors in vitro. I. Experimental histogenesis and quantitative analysis. Dev Biol. 1981 Jul 15;85(1):1–15. doi: 10.1016/0012-1606(81)90231-1. [DOI] [PubMed] [Google Scholar]
- Sweadner K. J. Post-translational modification and evoked release of two large surface proteins of sympathetic neurons. J Neurosci. 1983 Dec;3(12):2504–2517. doi: 10.1523/JNEUROSCI.03-12-02504.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tse A. G., Barclay A. N., Watts A., Williams A. F. A glycophospholipid tail at the carboxyl terminus of the Thy-1 glycoprotein of neurons and thymocytes. Science. 1985 Nov 29;230(4729):1003–1008. doi: 10.1126/science.2865810. [DOI] [PubMed] [Google Scholar]
- Williams A. F. Surface molecules and cell interactions. J Theor Biol. 1982 Sep 21;98(2):221–234. doi: 10.1016/0022-5193(82)90260-0. [DOI] [PubMed] [Google Scholar]
- van Agthoven A., Pierres M., Goridis C. Identification of a previously unrecognized polypeptide associated with lymphocyte function associated antigen one (LFA-1). Mol Immunol. 1985 Dec;22(12):1349–1358. doi: 10.1016/0161-5890(85)90056-2. [DOI] [PubMed] [Google Scholar]