Neogenin, an Avian Cell Surface Protein Expressed during Terminal Neuronal Differentiation, Is Closely Related to the Human Tumor Suppressor Molecule Deleted in Colorectal Cancer

• Published in: The Journal of cell biology Vol. 127; no. 6; pp. 2009 - 2020
• Main Authors: Vielmetter, Jost, Kayyem, Jon F., Roman, Janet M., Dreyer, William J.
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 01.12.1994; The Rockefeller University Press
• Subjects: Alternative Splicing; Amino Acid Sequence; Amino acids; Animals; Base Sequence; Cell Adhesion Molecules - genetics; Cell Differentiation; Cell growth; Cells; Cellular differentiation; Cerebellum - chemistry; Chick Embryo; Cloning, Molecular; Colorectal Neoplasms - genetics; Complementary DNA; DCC Receptor; DNA, Complementary - genetics; Genes, Tumor Suppressor - genetics; Immunoglobulins - genetics; Intestines - chemistry; Membrane proteins; Membrane Proteins - analysis; Membrane Proteins - genetics; Molecular Sequence Data; Molecules; Nerve Tissue - growth & development; Neurons; Neurons - chemistry; Optic Nerve - chemistry; Polymerase chain reaction; Protein Conformation; Proteins - classification; Receptors, Cell Surface; Retina - chemistry; RNA; RNA, Messenger - genetics; Sequence Homology, Amino Acid; Tissue Distribution; Tumor Suppressor Proteins
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.127.6.2009

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.