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Published March 1992 | public
Journal Article

Thy-1 Involvement in Neurite Outgrowth: Perturbation by Antibodies, Phospholipase C, and Mutation

Abstract

Thy-1 is a major cell surface protein anchored in the plasma membrane of neurons and lymphocytes by a covalent glycophosphotidylinositide linkage. Despite thorough characterization of the molecule's physicochemical properties, its biological function remains elusive. In this study we demonstrate that (i) monoclonal antibodies directed against Thy-1 are capable of enhancing neurite outgrowth from sympathetic neurons in culture, as well as stimulating the initiation of neurite sprouting from cultured adrenal chromaffin cells and PC12 cells. This effect is not observed with monovalent, Fab antibody fragments. Treatment with intact antibodies also results in the shedding of Thy-1 into the culture medium. (ii) Treatment of chromaffin cells with phosphotidylinositol-specific phospholipase C also results in an induction of neurite sprouting. The lipase effect can be blocked by preincubating the cells with monovalent anti-Thy-1 Fab fragments, indicating that the outgrowth stimulation is specifically due to removal of Thy-1. (iii) An entirely different approach to elucidating the function of Thy-1 involves mutagenesis of PC12 cells. Selection for Thy-1-deficient mutants revealed that cells lacking Thy-1 sprout neurites spontaneously at a very high frequency. A novel role for Thy-1 is proposed wherein the results of the mutant cell studies are compatible with the antibody and lipase data. Each of the perturbations can be viewed as releasing an inhibition that Thy-1 normally exerts on neurite outgrowth. We suggest that Thy-1 normally acts to stabilize neuronal membranes and processes, possibly through homophilic interactions.

Additional Information

© 1992 Academic Press, Inc. Accepted 22 November 1991. The authors thank Drs. Colin Barnstable, Irving Weissman, and Alan Williams for the kind gift of the mAbs 2Gl2, 19XE5, and OX-7, respectively; Dr. William Matthew for the gift of the pg22 hybridoma cell line; Doreen McDowell for the provision of culture media and collagen; Josette Carnahan for purifying the NGF; Drs. David Anderson, Zaven Kaprielian, and Ann Kato for their comments on the manuscript; and Lynnette Strobel for secretarial assistance. This work was supported by an NSF Graduate Fellowship to N.K.M. and a McKnight Foundation Neuroscience Research Award to P.H.P.

Additional details

Created:
August 20, 2023
Modified:
October 17, 2023