JAM4, a junctional cell adhesion molecule interacting with a tight junction protein, MAGI-1.
MAGI-1 is a membrane-associated guanylate kinase protein at tight junctions in epithelial cells. It interacts with various molecules and functions as a scaffold protein at cell junctions. We report here a novel MAGI-1-binding protein that we named junctional adhesion molecule 4 (JAM4). JAM4 belongs to an immunoglobulin protein family. JAM4 was colocalized with ZO-1 in kidney glomeruli and in intestinal epithelial cells. Biochemical in vitro studies revealed that JAM4 bound to MAGI-1 but not to ZO-1, whereas JAM1 did not bind to MAGI-1. JAM4 and MAGI-1 interacted with each other and formed clusters in COS-7 cells when coexpressed. JAM4 mediated calcium-independent homophilic adhesion and was accumulated at cell-cell contacts when expressed in L cells. MAGI-1, ZO-1, and occludin were recruited to JAM4-based cell contacts. JAM4 also reduced the permeability of CHO cell monolayers. MAGI-1 strengthened JAM4-mediated cell adhesion in L cells and sealing effects in CHO cells. These findings suggest that JAM4 together with MAGI-1 provides an adhesion machinery at tight junctions, which may regulate the permeability of kidney glomerulus and small intestinal epithelial cells.
Hirabayashi
Susumu
S
Department of Medical Biochemistry, Graduate School of Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8519, Japan.
Tajima
Makiko
M
Yao
Ikuko
I
Nishimura
Wataru
W
Mori
Hiroki
H
Hata
Yutaka
Y
D000256:Adenoviridae / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D019921:Biotinylation; D015152:Blotting, Northern; D016466:CHO Cells; D019556:COS Cells; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000737:chemistry* / Q000378:metabolism*; D002460:Cell Line; D003094:Collagen / Q000378:metabolism; D006224:Cricetinae; D004847:Epithelial Cells / Q000166:cytology; D005822:Genetic Vectors; D005982:Glutathione Transferase / Q000378:metabolism; D006031:Glycosylation; D051528:Guanylate Kinases; D007136:Immunoglobulins / Q000378:metabolism; D007150:Immunohistochemistry; D007422:Intestines / Q000166:cytology; D007678:Kidney Glomerulus / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D016253:Microscopy, Immunoelectron; D008969:Molecular Sequence Data; D009703:Nucleoside-Phosphate Kinase / Q000378:metabolism*; D010802:Phylogeny; D011233:Precipitin Tests; D011485:Protein Binding; D014176:Protein Biosynthesis; D012190:Retroviridae / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D013347:Subcellular Fractions / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques
D015815:Cell Adhesion Molecules; C475024:Igsf5 protein, mouse; D007136:Immunoglobulins; D003094:Collagen; D005982:Glutathione Transferase; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases