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J. Biol. Chem., Vol. 276, Issue 10, 7337-7345, March 9, 2001

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CALEB Binds via Its Acidic Stretch to the Fibrinogen-like Domain of Tenascin-C or Tenascin-R and Its Expression Is Dynamically Regulated after Optic Nerve Lesion^*

Stefan Schumacher^§, Marion Jung^¶, Ursel Nörenberg, Armin Dorner, Ruth Chiquet-Ehrismann, Claudia A. O. Stuermer^¶, and Fritz G. Rathjen^**

From the  Max-Delbrück-Centrum für Molekulare Medizin, Robert-Rössle-Strasse 10, D-13092 Berlin, Germany, ^¶ Fachbereich Biologie, Universität Konstanz, D-78457 Konstanz, Germany, and  Friedrich Miescher Institut, P. O. Box 2543, CH-4002 Basel, Switzerland

Recently, we described a novel chick neural transmembrane glycoprotein, which interacts with the extracellular matrix proteins tenascin-C and tenascin-R. This protein, termed CALEB, contains an epidermal growth factor-like domain and appears to be a novel member of the epidermal growth factor family of growth and differentiation factors. Here we analyze the interaction between CALEB and tenascin-C as well as tenascin-R in more detail, and we demonstrate that the central acidic peptide segment of CALEB is necessary to mediate this binding. The fibrinogen-like globe within tenascin-C or -R enables both proteins to bind to CALEB. We show that two isoforms of CALEB in chick and rodents exist that differed in their cytoplasmic segments. To begin to understand the in vivo function of CALEB and since in vitro antibody perturbation experiments indicated that CALEB might be important for neurite formation, we analyzed the expression pattern of the rat homolog of CALEB during development of retinal ganglion cells, after optic nerve lesion and during graft-assisted retinal ganglion cell axon regeneration by in situ hybridization. These investigations demonstrate that CALEB mRNA is dynamically regulated after optic nerve lesion and that this mRNA is expressed in most developing and in one-third of the few regenerating (GAP-43 expressing) retinal ganglion cells.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EMBL Data Bank with accession number(s) AF292101 and AF292102.

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