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PMID: 1618903 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Different extracellular domains of the neural cell adhesion molecule (N-CAM) are involved in different functions.

The Journal of cell biology ·Vol. 118 ·No. 1 ·1992-07-00 ·Pages 177-94

Frei T, von Bohlen und Halbach F, Wille W, Schachner M

Abstract

The neural cell adhesion molecule (N-CAM) engages in diverse functional roles in neural cell interactions. Its extracellular part consists of five Ig-like domains and two fibronectin type III homologous (type III) repeats. To investigate the functional properties of the different structural domains of the molecule in cell interactions and signal transduction to the cell interior, we have synthesized, in a bacterial expression system, the individual domains and tandem sets of individual domains as protein fragments. These protein fragments were tested for their capacity to influence adhesion and spreading of neuronal cell bodies, promote neurite outgrowth, and influence cellular migration patterns from cerebellar microexplants in vitro. Ig-like domains I and II and the combined type III repeats I-II were most efficient for adhesion of neuronal cell bodies, when coated as substrates. Neurite outgrowth was best on the substrate-coated combined type III repeats I-II, followed by the combined Ig-like domains I-V and Ig-like domain I. Spreading of neuronal cell bodies was best on substrate-coated combined type III repeats I-II, followed by Ig-like domain I and the combined Ig-like domains I-V. The cellular migration pattern from cerebellar microexplant cultures plated on a mixture of laminin and poly-L-lysine was modified by Ig-like domains I, III, and IV, while Ig-like domains II and V and the combined type III repeats I-II did not show significant modifications, when added as soluble fragments. Outgrowth of astrocytic processes from the explant core was influenced only by Ig-like domain I. Metabolism of inositol phosphates was strongly increased by Ig-like domain I and less by the Ig-like domains II, III, IV, and V, and not influenced by the combined type III repeats I-II. Intracellular concentrations of Ca2+ and pH values were increased only by the Ig-like domains I and II. Intracellular levels of cAMP and GMP were not influenced by any protein fragment. These experiments indicate that different domains of N-CAM subserve different functional roles in cell recognition and signal transduction, and are functionally competent without nervous system-derived carbohydrate structures.

MeSH Terms
Animals Calcium/metabolism Cell Adhesion/drug effects,physiology Cell Adhesion Molecules, Neuronal/genetics,metabolism Cell Movement/drug effects,physiology Cells, Cultured Cerebellum/growth & development Cloning, Molecular Mice Mice, Inbred ICR Neurites/drug effects,metabolism Neurons/drug effects,metabolism Peptide Fragments/genetics,metabolism,pharmacology Recombinant Proteins/biosynthesis Second Messenger Systems/physiology Signal Transduction Structure-Activity Relationship
Chemicals
Cell Adhesion Molecules, Neuronal Peptide Fragments Recombinant Proteins Calcium
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Frei T
Department of Neurobiology, Swiss Federal Institute of Technology, Hönggerberg, Zürich.
von Bohlen und Halbach F
Wille W
Schachner M
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.118.1.177
Published
1992-07-00
Pages
177-94
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2289517
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.118.1.177 PMC Full Text View journal details
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