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© The Rockefeller University Press, 0021-9525/1999//865 $5.00
The Journal of Cell Biology, Volume 145, Number 4, , 1999 865-876


Regular Articles

Neurotractin, A Novel Neurite Outgrowth-promoting Ig-like Protein that Interacts with CEPU-1 and LAMP



Andreas Marg*, Pinar Sirim{ddagger}, Frank Spaltmann{ddagger}, Antonius Plagge{ddagger},§, Gunther Kauselmann||, Friedrich Buck||, Fritz G. Rathjen*, and Thomas Brümmendorf*,{ddagger}

* Max-Delbrück-Center for Molecular Medicine, D-13092 Berlin, Germany; {ddagger} Max-Planck-Institute for Developmental Biology, D-72076 Tübingen, Germany; § The Babraham Institute, Cambridge CB2 4AT, England; and || Center for Molecular Neurobiology, University of Hamburg, D-22529 Hamburg, Germany

The formation of axon tracts in nervous system histogenesis is the result of selective axon fasciculation and specific growth cone guidance in embryonic development. One group of proteins implicated in neurite outgrowth, fasciculation, and guidance is the neural members of the Ig superfamily (IgSF). In an attempt to identify and characterize new proteins of this superfamily in the developing nervous system, we used a PCR-based strategy with degenerated primers that represent conserved sequences around the characteristic cysteine residues of Ig-like domains. Using this approach, we identified a novel neural IgSF member, termed neurotractin. This GPI-linked cell surface glycoprotein is composed of three Ig-like domains and belongs to the IgLON subgroup of neural IgSF members. It is expressed in two isoforms with apparent molecular masses of 50 and 37 kD, termed L-form and S-form, respectively. Monoclonal antibodies were used to analyze its biochemical features and histological distribution. Neurotractin is restricted to subsets of developing commissural and longitudinal axon tracts in the chick central nervous system. Recombinant neurotractin promotes neurite outgrowth of telencephalic neurons and interacts with the IgSF members CEPU-1 (KD = 3 x 10–8 M) and LAMP. Our data suggest that neurotractin participates in the regulation of neurite outgrowth in the developing brain.

Key Words: cell adhesion • development • Ig superfamily • neurite outgrowth • nervous system



Abbreviations used in this paper: ALF, automated laser fluorescent; IgLON, LAMP/OBCAM/neurotrimin subgroup of the IgSF; IgSF, immunoglobulin superfamily; LAMP, limbic system-associated membrane protein; NgCAM, neuron-glia cell adhesion molecule; NrCAM, NgCAM-related cell adhesion molecule; OBCAM, opioid binding cell adhesion molecule; PI-PLC, phosphatidylinositol-specific phospholipase C; RT, room temperature.

This study was in part supported by grant SFB 515 (Deutsche Forschungsgemeinschaft) to F.G. Rathjen and by grant Br1217/3-1 (Deutsche Forschungsgemeinschaft) to T. Brümmendorf.

Pinar Sirim's current address is GeneCenter, University of Munich, Munich, Germany.

Frank Spaltmann's current address is BAYER AG, Pharma Research, Wuppertal, Germany.

Gunther Kauselmann's current address is Artemis Pharmaceuticals, Cologne, Germany.

Friedrich Buck's current address is Institute for Cell Biochemistry and Clinical Neurobiology, University of Hamburg, Hamburg, Germany.



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