title: Enhanced nerve-mast cell interaction by a neuronal short isoform of cell adhesion molecule-1.
abstract: Close apposition of nerve and mast cells is viewed as a functional unit of neuro-immune mechanisms, and it is sustained by trans-homophilic binding of cell adhesion molecule-1 (CADM1), an Ig superfamily member. Cerebral nerve-mast cell interaction might be developmentally modulated, because the alternative splicing pattern of four (a-d) types of CADM1 transcripts drastically changed during development of the mouse cerebrum: developing cerebrums expressed CADM1b and CADM1c exclusively, while mature cerebrums expressed CADM1d additionally and predominantly. To probe how individual isoforms are involved in nerve-mast cell interaction, Neuro2a neuroblastoma cells that express CADM1c endogenously were modified to express additionally either CADM1b (Neuro2a-CADM1b) or CADM1d (Neuro2a-CADM1d), and they were cocultured with mouse bone marrow-derived mast cells (BMMCs) and BMMC-derived cell line IC-2 cells, both of which expressed CADM1c. BMMCs were found to adhere to Neuro2a-CADM1d neurites more firmly than to Neuro2a-CADM1b neurites when the adhesive strengths were estimated from the femtosecond laser-induced impulsive forces minimally required for detaching BMMCs. GFP-tagging and crosslinking experiments revealed that the firmer adhesion site consisted of an assembly of CADM1d cis-homodimers. When Neuro2a cells were specifically activated by histamine, intracellular Ca(2+) concentration was increased in 63 and 38% of CADM1c-expressing IC-2 cells that attached to the CADM1d assembly site and elsewhere, respectively. These results indicate that CADM1d is a specific neuronal isoform that enhances nerve-mast cell interaction, and they suggest that nerve-mast cell interaction may be reinforced as the brain grows mature because CADM1d becomes predominant.
authors.affiliation: Division of Molecular Pathology, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Man
authors.initials: M
authors.lastname: Hagiyama
authors.forename: Tadahide
authors.initials: T
authors.lastname: Furuno
authors.forename: Yoichiroh
authors.initials: Y
authors.lastname: Hosokawa
authors.forename: Takanori
authors.initials: T
authors.lastname: Iino
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ito
authors.forename: Takao
authors.initials: T
authors.lastname: Inoue
authors.forename: Mamoru
authors.initials: M
authors.lastname: Nakanishi
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Murakami
authors.forename: Akihiko
authors.initials: A
authors.lastname: Ito
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002450:Cell Communication; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D054022:Cerebrum / Q000166:cytology / Q000196:embryology / Q000254:growth & development / Q000276:immunology; D018920:Coculture Techniques; D006632:Histamine / Q000494:pharmacology; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism*; D008407:Mast Cells / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D016501:Neurites / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism
chemical_list: C498598:Cadm1 protein, mouse; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D020033:Protein Isoforms; D006632:Histamine; D002118:Calcium