The C-terminal region of NELL1 mediates osteoblastic cell adhesion through integrin α3β1.
NELL1 is a secretory osteogenic protein containing several structural motifs that suggest that it functions as an extracellular matrix component. To determine the mechanisms underlying NELL1-induced osteoblast differentiation, we examined the cell-adhesive activity of NELL1 using a series of recombinant NELL1 proteins. We demonstrated that NELL1 promoted osteoblastic cell adhesion through at least three cell-binding domains located in the C-terminal region of NELL1. Adhesion of cells to NELL1 was strongly inhibited by function-blocking antibodies against integrin α3 and β1 subunits, suggesting that osteoblastic cells adhered to NELL1 through integrin α3β1. Further, focal adhesion kinase activation is involved in NELL1 signaling.
Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa, Nagoya 464-8601, Japan.
Ai
A
Hasebe
Yoko
Y
Nakamura
Hiroki
H
Tashima
Kaneyoshi
K
Takahashi
Masumi
M
Iijima
Nobuo
N
Yoshimoto
Kang
K
Ting
Shun'ichi
S
Kuroda
Tomoaki
T
Niimi
D016475:3T3 Cells; D000818:Animals; D002135:Calcium-Binding Proteins / Q000737:chemistry* / Q000502:physiology; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000737:chemistry* / Q000502:physiology; D006801:Humans; D039201:Integrin alpha3beta1 / Q000096:biosynthesis*; D020935:MAP Kinase Signaling System; D051379:Mice; D008809:Mice, Inbred C3H; D008954:Models, Biological; D010006:Osteoblasts / Q000166:cytology*; D010957:Plasmids / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry; D015398:Signal Transduction
D002135:Calcium-Binding Proteins; D006023:Glycoproteins; D039201:Integrin alpha3beta1; C513122:Nell1 protein, mouse; D011994:Recombinant Proteins