The C-terminal region of NELL1 mediates osteoblastic cell adhesion through integrin α3β1

• Published in: FEBS letters Vol. 586; no. 16; pp. 2500 - 2506
• Main Authors: Hasebe, Ai, Nakamura, Yoko, Tashima, Hiroki, Takahashi, Kaneyoshi, Iijima, Masumi, Yoshimoto, Nobuo, Ting, Kang, Kuroda, Shun’ichi, Niimi, Tomoaki
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 30-07-2012
• Subjects: 3T3 Cells; Animals; Calcium-Binding Proteins - chemistry; Calcium-Binding Proteins - physiology; Cell Adhesion; Cell Line, Tumor; coiled-coil; Dose-Response Relationship, Drug; ECM; EGF; epidermal growth factor; ERK; Extracellular matrix; extracellular signal-regulated kinase; FAK; focal adhesion kinase; Gene Expression Regulation; Glycoproteins - chemistry; Glycoproteins - physiology; Humans; Integrin alpha3beta1 - biosynthesis; MAP Kinase Signaling System; MAPK; Mice; Mice, Inbred C3H; mitogen-activated protein kinase; Models, Biological; N-terminal thrombospondin-1-like; NELL-1; Osteoblast differentiation; Osteoblasts - cytology; Plasmids - metabolism; Protein Structure, Tertiary; Recombinant Proteins - chemistry; Signal Transduction; TSPN; von Willebrand factor type C; VWC; CC; FAK; NELL-1; VWC; EGF; Cell adhesion; Extracellular matrix; TSPN; MAPK; ECM; ERK; Osteoblast differentiation
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2012.06.014

► NELL1 promotes osteoblastic cell adhesion. ► Three cell-binding sites are localized to the C-terminal region of NELL1. ► Integrin α3β1 is the major receptor for osteoblastic cell adhesion onto NELL1. ► FAK-MAPK pathway is involved in NELL1 signaling.
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.