Neogenin, an Avian Cell Surface Protein Expressed during Terminal Neuronal Differentiation, Is Closely Related to the Human Tumor Suppressor Molecule Deleted in Colorectal Cancer
Using a monoclonal antibody, we have identified and characterized a previously unknown cell surface protein in chicken that we call neogenin and have determined its primary sequence. The deduced amino acid sequence and structure of neogenin characterize it as a member of the immunoglobulin (Ig) superfamily. Based on amino acid sequence similarities, neogenin is closely related to the human tumor suppressor molecule DCC (deleted in colorectal cancer). Neogenin and DCC define a subgroup of Ig superfamily proteins structurally distinct from other Ig molecules such as N-CAM, Ng-CAM, and Bravo/Nr-CAM. As revealed by antibody staining of tissue sections and Western blots, neogenin expression correlates with the onset of neuronal differentiation. Neogenin is also found on cells in the lower gastrointestinal tract of embryonic chickens. DCC has been observed in human neural tissues and has been shown to be essential for terminal differentiation of specific cell types in the adult human colon. These parallels suggest that neogenin, like DCC, is functionally involved in the transition from cell proliferation to terminal differentiation of specific cell types. Since neogenin is expressed on growing neurites and downregulated at termination of neurite growth, it may also play an important role in many of the complex functional aspects of neurite extension and intercellular signaling.
© 1994 Rockefeller University Press. Received for publication 15 March 1994 and in revised form 19 September 1994. Published December 15, 1994. We thank Inder Nangiana, Susan Ou, and Jennifer Kim for their excellent technical assistance, Uli Schwarz for his support for initiation of this project during our visit in Tübingen, Peter Sonderegger and Richard Zuellig for kindly providing us with an El4 chicken ⋋-ZAPII cDNA library, Hirdeypal Bhathal for kindly providing us with a chicken genomic-FIXII library, and Paul Patterson for critically reading the manuscript. Jost Vielmetter was supported in part by a fellowship from Deutsche Forschungs Gemeinschaft (Germany). This work was also supported by the National Institutes of Health grant EY07725.
Published - VIEjcb94.pdf