Mechanism of homophilic binding mediated by ninjurin, a novel widely expressed adhesion molecule.
Ninjurin is a novel protein that is up-regulated after nerve injury both in dorsal root ganglion (DRG) neurons and in Schwann cells. We previously reported that ninjurin demonstrates properties of a homophilic adhesion molecule and promotes neurite outgrowth from primary cultured DRG neurons. We have now found that ninjurin is widely expressed in both adult and embryonic tissues, primarily in those of epithelial origin. Aggregation assays were used to demonstrate that ninjurin-mediated adhesion requires divalent cations and is an energy-dependent process. The critical domain for ninjurin-mediated homophilic adhesion was localized to an 11-residue region (between Pro26 and Asn37) by mutagenesis and by employing synthetic oligopeptides as competitive inhibitors of ninjurin-mediated adhesion. Of particular importance are the Trp residue at position 29 and the 3 arginines in the region. Furthermore, we show that the peptide which inhibits aggregation of Jurkat cells expressing ninjurin is also capable of blocking the ability of ninjurin to promote neurite extension from DRG neurons. Using FISH analysis, the ninjurin gene was localized to human chromosome 9q22. Several genetic diseases of unknown etiology have been mapped to this region, including hereditary sensory neuropathy type 1, self-healing squamous epithelioma, split-hand/foot deformity type 1, and familial dilated cardiomyopathy.
Araki
T
T
Division of Laboratory Medicine, Department of Pathology and Medicine, Washington University Medical School, St. Louis, Missouri 63110, USA.
Zimonjic
D B
DB
Popescu
N C
NC
Milbrandt
J
J
D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000648:ultrastructure; D001667:Binding, Competitive; D015816:Cell Adhesion Molecules, Neuronal / Q000737:chemistry / Q000378:metabolism*; D002449:Cell Aggregation; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9; D004848:Epithelium / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D017403:In Situ Hybridization; D017404:In Situ Hybridization, Fluorescence; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000737:chemistry / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D015816:Cell Adhesion Molecules, Neuronal; C484438:NINJ1 protein, human; D009414:Nerve Growth Factors; C101196:Ninj1 protein, rat; D010455:Peptides; D012333:RNA, Messenger