Collapsin response mediator proteins of neonatal rat brain interact with chondroitin sulfate.
Chondroitin sulfate proteoglycans are structurally and functionally important components of the extracellular matrix of the central nervous system. Their expression in the developing mammalian brain is precisely regulated, and cell culture experiments implicate these proteoglycans in the control of cell adhesion, neuron migration, neurite formation, neuronal polarization, and neuron survival. Here, we report that a monoclonal antibody against chondroitin sulfate-binding proteins from neonatal rat brain recognizes collapsin response mediator protein-4 (CRMP-4), which belongs to a family of proteins involved in collapsin/semaphorin 3A signaling. Soluble CRMPs from neonatal rat brain bound to chondroitin sulfate affinity columns, and CRMP-specific antisera co-precipitated chondroitin sulfate. Moreover, chondroitin sulfate and CRMP-4 were found to be localized immuno-histochemically in overlapping distributions in the marginal zone and the subplate of the cerebral cortex. CRMPs are released to culture supernatants of NTera-2 precursor cells and of neocortical neurons after cell death, and CRMP-4 is strongly expressed in the upper cortical plate of neonatal rat where cell death is abundant. Therefore, naturally occurring cell death is a plausible mechanism that targets CRMPs to the extracellular matrix at certain stages of development. In summary, our data indicate that CRMPs, in addition to their role as cytosolic signal transduction molecules, may subserve as yet unknown functions in the developing brain as ligands of the extracellular matrix.
Franken
Sebastian
S
Rheinische Friedrich-Wilhelms-Universität Bonn, Institut für Physiologische Chemie, Nussallee 11, D-53115 Bonn, Germany.
Junghans
Ulrich
U
Rosslenbroich
Volker
V
Baader
Stephan L
SL
Hoffmann
Ralf
R
Gieselmann
Volkmar
V
Viebahn
Christoph
C
Kappler
Joachim
J
D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D002809:Chondroitin Sulfates / Q000378:metabolism*; D002846:Chromatography, Affinity; D017931:DNA Primers; D006025:Glycosaminoglycans; D006493:Heparin; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D019579:Neocortex / Q000166:cytology / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry; D016133:Polymerase Chain Reaction; D051381:Rats; D017208:Rats, Wistar; D021241:Spectrometry, Mass, Electrospray Ionization
D000911:Antibodies, Monoclonal; D017931:DNA Primers; C449760:Dpysl3 protein, rat; D006025:Glycosaminoglycans; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D006493:Heparin; D002809:Chondroitin Sulfates