BT‐IgSF, a novel immunoglobulin superfamily protein, functions as a cell adhesion molecule

Abstract

BT-IgSF is a newly identified cell surface glycoprotein belonging to the immunoglobulin superfamily (IgSF). We have previously shown that the expression of the BT-IgSF gene was highly restricted to brain and testis, and its transcript was detected in both neurons and glial cells. In this study, to explore its function, we generated cells overexpressing BT-IgSF proteins and analyzed their phenotypes. We found that the constitutive expression of BT-IgSF in the myeloid leukemia cell line TF-1-fms did not alter the growth rates, but caused the formation of large cell aggregates. The cell aggregates were also observed with mutant BT-IgSF lacking its cytoplasmic tail, the amino acid sequences of which were highly conserved among the BT-IgSF subgroup proteins. The neutralizing antibody to beta(1) integrin did not diminish the cell aggregate formation. These results indicate that BT-IgSF functions as a cell adhesion molecule, that its cytoplasmic tail is not essential for the function, and that beta(1) integrin is not involved in the function. We confirmed the cell adhesion function using NIH/3T3 fibroblastic cells expressing BT-IgSF in an inducible system. Flow cytometric analyses with the cells demonstrated that the cell aggregation mediated by BT-IgSF was through homophilic molecular interaction, and in a Ca(2+)/Mg(2+)-independent manner. Coupled with its restricted pattern of the expression, the cell adhesion-inducing function of BT-IgSF suggests a role of the cell surface molecule in the development/function of the central nervous system and spermatogenesis.

Melanophore Migration and Survival during Zebrafish Adult Pigment Stripe Development Require the Immunoglobulin Superfamily Adhesion Molecule Igsf11

“…Mammalian IGSF11 mediates homophilic adhesive interactions in vitro [59] and such interactions could occur in vivo during adult pigment pattern formation. Yet, our findings that Igsf11 acts autonomously to melanophores or their precursors in cell transplantation and genetic rescue experiments, and that igsf11 transcripts and protein are not detected in the environment through which these cells migrate, suggest that Igsf11 interacts with one or more heterophilic binding partners to promote melanophore lineage morphogenesis.…”

The coxsackie- and adenovirus receptor (CAR) is an in vivo marker for epithelial tight junctions, with a potential role in regulating permeability and tissue homeostasis

“…It serves as the primary attachment protein for entry of the two viruses into cells. Members of the CTX subfamily include CTX (cortical thymocyte marker in Xenopus) and its human and rodent homologues CTH and CTM [5,6], A33 [7,8], JAMs (junctional adhesion molecules A, B, C, JAM-4 and JAML) [9,10], ESAM (endothelial cell-selective adhesion molecule) [11,12], BT-IgSF (brain-testis IgSF) [13,14] and CLMP (CAR-like membrane protein; also named adipocyte adhesion molecule, ACAM) [15,16]. They all possess a common structure in the extracellular domain, with one V and one C2 Ig-loop and in most cases two cysteines that form a disulfide-linked loop encompassing C2.…”

Ectoplasmic specialization: a friend or a foe of spermatogenesis?

“…(28) BT-IgSF and CLMP both mediate homotypic adhesion between cells. (28,29) While these TJ proteins are crucial to confer a paracellular barrier to limit the passage of substances across the cell epithelium, there are other proteins that strengthen BTB integrity at the tricellular contact interface. For instance, a newly identified TJ protein called tricellulin was found to be expressed in testes, and localized at the interface of cells in small intestine, kidney and lung.…”