The surface glycoprotein, Thy-1, when expressed by transfection in NG115/401L neural cells, inhibits their neurite outgrowth over astrocytes. We have investigated the role of the glycosylphosphatidylinositol anchor of Thy-1 in this inhibition. Hybrid molecules, in which the lipid anchor was replaced by polypeptide transmembrane domains, were expressed by transfection. Lines expressing Thy-1 with the transmembrane and full cytoplasmic domains of NCAM-140, or with the transmembrane and truncated cytoplasmic domain of CD8, were not inhibited in their ability to extend neurites over astrocytes. Truncation of the cytoplasmic domain of NCAM-140 to just two amino acids, however, produced a transmembrane form of Thy-1 that, when expressed at high levels, inhibited neurite outgrowth. All forms of Thy-1 were concentrated in clusters that occurred primarily on fine filopodia. In double transfectants expressing normal Thy-1 and Thy-1 with the full NCAM cytoplasmic tail, the clusters of each form were separate, with no instances of the transmembrane form being found within the clusters of lipid-anchored Thy-1. Thy-1 with the two-amino-acid cytoplasmic domain of NCAM also occurred in clusters separate from those occupied by lipid-anchored Thy-1, but substantial ‘invasion’ of the clusters of normal Thy-1 by this transmembrane construct occurred. We suggest that the ability of this hybrid protein to enter the lipid-anchored clusters enables it to activate the signalling pathways that normal Thy-1 uses. Thus the membrane anchor, in targetting Thy-1 to different microdomains on the cell surface, determines its ability to inhibit neurite outgrowth on astrocytes.
The mode of anchorage to the cell surface determines both the function and the membrane location of Thy-1 glycoprotein
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M.C. Tiveron, M. Nosten-Bertrand, H. Jani, D. Garnett, E.M. Hirst, F. Grosveld, R.J. Morris; The mode of anchorage to the cell surface determines both the function and the membrane location of Thy-1 glycoprotein. J Cell Sci 1 July 1994; 107 (7): 1783–1796. doi: https://doi.org/10.1242/jcs.107.7.1783
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