Domain and functional analysis of a novel platelet-endothelial cell surface protein, SCUBE

Cheng Fen Tu, Yu Ting Yan, Szu Yao Wu, Bambang Djoko, Ming Tzu Tsai, Chien Jui Cheng, Ruey Bing Yang

Research output: Contribution to journalArticle

64 Citations (Scopus)

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 languageEnglish
Pages (from-to)12478-12488
Number of pages11
JournalJournal of Biological Chemistry
Volume283
Issue number18
DOIs
Publication statusPublished - May 2 2008

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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