Abstract
SCUBE1 (signal peptide-CUB-EGF domain-containing protein 1) is a novel, secreted, cell surface glycoprotein expressed during early embryogenesis and found in platelet and endothelial cells. This protein is composed of an N-terminal signal peptide sequence followed by nine tandemly arranged epidermal growth factor (EGF)-like repeats, a spacer region, three cysteine-rich repeat motifs, and one CUB domain at the C terminus. However, little is known about its domain and biological function. Here, we generated a comprehensive panel of domain deletion constructs and a new genetic mouse model with targeted disruption of Scube1 (Scube1Δcub/Δcub) to investigate the domain function and biological significance. A number of cell-based assays were utilized to define the critical role of the spacer region for membrane association and establish that the EGF-like repeats 7-9 are sufficient for the formation of SCUBE1-mediated homophilic adhesions in a calcium-dependent fashion. Biochemical and molecular analyses showed that the C-terminal cysteine-rich motifs and CUB domain could directly bind and antagonize the bone morphogenetic protein activity. Furthermore, genetic ablation of this C-terminal region resulted in brain malformation in the Scube1 Δcub/Δcub embryos. Together, our results support the dual roles of SCUBE1 on brain morphogenesis and cell-cell adhesions through its distinct domain function.
| Original language | English |
|---|---|
| Pages (from-to) | 12478-12488 |
| Number of pages | 11 |
| Journal | Journal of Biological Chemistry |
| Volume | 283 |
| Issue number | 18 |
| DOIs | |
| Publication status | Published - May 2 2008 |
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ASJC Scopus subject areas
- Biochemistry
- Cell Biology
- Molecular Biology
Cite this
Domain and functional analysis of a novel platelet-endothelial cell surface protein, SCUBE. / Tu, Cheng Fen; Yan, Yu Ting; Wu, Szu Yao; Djoko, Bambang; Tsai, Ming Tzu; Cheng, Chien Jui; Yang, Ruey Bing.
In: Journal of Biological Chemistry, Vol. 283, No. 18, 02.05.2008, p. 12478-12488.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Domain and functional analysis of a novel platelet-endothelial cell surface protein, SCUBE
AU - Tu, Cheng Fen
AU - Yan, Yu Ting
AU - Wu, Szu Yao
AU - Djoko, Bambang
AU - Tsai, Ming Tzu
AU - Cheng, Chien Jui
AU - Yang, Ruey Bing
PY - 2008/5/2
Y1 - 2008/5/2
N2 - SCUBE1 (signal peptide-CUB-EGF domain-containing protein 1) is a novel, secreted, cell surface glycoprotein expressed during early embryogenesis and found in platelet and endothelial cells. This protein is composed of an N-terminal signal peptide sequence followed by nine tandemly arranged epidermal growth factor (EGF)-like repeats, a spacer region, three cysteine-rich repeat motifs, and one CUB domain at the C terminus. However, little is known about its domain and biological function. Here, we generated a comprehensive panel of domain deletion constructs and a new genetic mouse model with targeted disruption of Scube1 (Scube1Δcub/Δcub) to investigate the domain function and biological significance. A number of cell-based assays were utilized to define the critical role of the spacer region for membrane association and establish that the EGF-like repeats 7-9 are sufficient for the formation of SCUBE1-mediated homophilic adhesions in a calcium-dependent fashion. Biochemical and molecular analyses showed that the C-terminal cysteine-rich motifs and CUB domain could directly bind and antagonize the bone morphogenetic protein activity. Furthermore, genetic ablation of this C-terminal region resulted in brain malformation in the Scube1 Δcub/Δcub embryos. Together, our results support the dual roles of SCUBE1 on brain morphogenesis and cell-cell adhesions through its distinct domain function.
AB - SCUBE1 (signal peptide-CUB-EGF domain-containing protein 1) is a novel, secreted, cell surface glycoprotein expressed during early embryogenesis and found in platelet and endothelial cells. This protein is composed of an N-terminal signal peptide sequence followed by nine tandemly arranged epidermal growth factor (EGF)-like repeats, a spacer region, three cysteine-rich repeat motifs, and one CUB domain at the C terminus. However, little is known about its domain and biological function. Here, we generated a comprehensive panel of domain deletion constructs and a new genetic mouse model with targeted disruption of Scube1 (Scube1Δcub/Δcub) to investigate the domain function and biological significance. A number of cell-based assays were utilized to define the critical role of the spacer region for membrane association and establish that the EGF-like repeats 7-9 are sufficient for the formation of SCUBE1-mediated homophilic adhesions in a calcium-dependent fashion. Biochemical and molecular analyses showed that the C-terminal cysteine-rich motifs and CUB domain could directly bind and antagonize the bone morphogenetic protein activity. Furthermore, genetic ablation of this C-terminal region resulted in brain malformation in the Scube1 Δcub/Δcub embryos. Together, our results support the dual roles of SCUBE1 on brain morphogenesis and cell-cell adhesions through its distinct domain function.
UR - http://www.scopus.com/inward/record.url?scp=45549096967&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=45549096967&partnerID=8YFLogxK
U2 - 10.1074/jbc.M705872200
DO - 10.1074/jbc.M705872200
M3 - Article
C2 - 18303018
AN - SCOPUS:45549096967
VL - 283
SP - 12478
EP - 12488
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 18
ER -