Discoidin domain of Del1 protein contributes to its deposition in the extracellular matrix.
The extracellular matrix (ECM) acts as a critical factor during morphogenesis. Because the organization of the ECM directly influences the structure of tissues and organs, a determination of the way that ECM organization is regulated should help to clarify morphogenesis. We have analyzed the assembly of Del1, an ECM protein produced by endothelial cells in embryos, in the ECM. Del1 consists of three epidermal growth factor repeats (E1-E3) at its N-terminus and two discoidin domains (C1, C2) at its C-terminus. Experiments with various deletion mutants of Del1 have revealed that fragments containing the C-terminus of C1, which has a lectin-like structure, direct deposition in the ECM. The efficiency of deposition varies according to the presence of other domains in Del1. A fragment containing E3 and C1 has the strongest deposition activity, whereas fragments containing C2, which is highly homologous to C1, have low deposition activity. Digestion of ECM with hyaluronidase from bovine testis releases Del1 from the ECM, suggesting that glycosaminoglycans are involved in the deposition of Del1. In vivo gene transfer experiments have shown that fusion with the deposition domain of Del1 dramatically alters the distribution of exogenous proteins in mice. Thus, the extent of Del1 deposition may modify the organization of the ECM.
Hidai
Chiaki
C
Research Center for Advanced Medicine, Nihon University School of Medicine, Tokyo, Japan. hidai@med.nihon-u.ac.jp
Kawana
Masatoshi
M
Kitano
Hisataka
H
Kokubun
Shinichiro
S
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D019556:COS Cells; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D015815:Cell Adhesion Molecules; D002460:Cell Line; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003412:Cricetulus; D005109:Extracellular Matrix / Q000378:metabolism*; D017353:Gene Deletion; D050939:Gene Fusion; D018014:Gene Transfer Techniques; D000882:Haplorhini; D006821:Hyaluronoglucosaminidase / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008969:Molecular Sequence Data; D017384:Sequence Deletion; D015017:Yolk Sac / Q000166:cytology / Q000502:physiology
D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; C491706:Edil3 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D006821:Hyaluronoglucosaminidase