STRUCTURE AND EXPRESSION OF FIBRILLIN-2, A NOVEL MICROFIBRILLAR COMPONENT PREFERENTIALLY LOCATED IN ELASTIC MATRICES

被引:322
作者
ZHANG, H
APFELROTH, SD
HU, W
DAVIS, EC
SANGUINETI, C
BONADIO, J
MECHAM, RP
RAMIREZ, F
机构
[1] MT SINAI SCH MED,BROOKDALE CTR MOLEC BIOL,NEW YORK,NY 10029
[2] NYU,SCH MED,DEPT PATHOL,NEW YORK,NY 10016
[3] WASHINGTON UNIV,MED CTR,DEPT CELL BIOL,ST LOUIS,MO 63110
[4] WASHINGTON UNIV,MED CTR,DEPT MED,ST LOUIS,MO 63110
[5] UNIV MICHIGAN,MED CTR,DEPT PATHOL,ANN ARBOR,MI 48109
关键词
D O I
10.1083/jcb.124.5.855
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
During the previous cloning of the fibrillin gene (FBN1), we isolated a partial cDNA coding for a fibrillin-like peptide and mapped the corresponding gene (FBN2) to human chromosome 5. (Lee, B., M. Godfrey, E. Vitale, H. Hori, M. G. Mattei, M. Sarfarazi, P. Tsipouras, F Ramirez, and D. W Hollister. 1991. Nature [Lond]. 352:330-334). The study left, however, unresolved whether or not the FBN2 gene product is an extracellular component structurally related to fibrillin. Work presented in this report clarifies this important point. Determination of the entire primary structure of the FBN2 gene product demonstrated that this polypeptide is highly homologous to fibrillin. Immunoelectron microscopy localized both fibrillin proteins to elastin-associated extracellular microfibrils. Finally, immunohistochemistry revealed that the fibrillins co-distribute in elastic and nonelastic connective tissues of the developing embryo, with preferential accumulation of the FBN2 gene product in elastic fiber-rich matrices. These results support the original hypothesis that the fibrillins may have distinct but related functions in the formation and maintenance of extracellular microfibrils. Accordingly, we propose to classify the FBN1 and FBN2 gene products as a new family of extracellular proteins and to name its members fibrillin-1 and fibrillin-2, respectively.
引用
收藏
页码:855 / 863
页数:9
相关论文
共 35 条
  • [1] BEALS RK, 1971, J BONE JOINT SURG AM, V53, P887
  • [2] CHEN YP, 1993, J BIOL CHEM, V268, P27381
  • [3] CLAASSEN LA, 1991, J BIOL CHEM, V266, P11388
  • [4] CLEARY EG, 1983, INT REV CONNECT TISS, V10, P97
  • [5] FIBRILLIN BINDS CALCIUM AND IS CODED BY CDNAS THAT REVEAL A MULTIDOMAIN STRUCTURE AND ALTERNATIVELY SPLICED EXONS AT THE 5' END
    CORSON, GM
    CHALBERG, SC
    DIETZ, HC
    CHARBONNEAU, NL
    SAKAI, LY
    [J]. GENOMICS, 1993, 17 (02) : 476 - 484
  • [6] DAVIS C G, 1990, New Biologist, V2, P410
  • [7] Dietz Harry C., 1992, Human Mutation, V1, P366, DOI 10.1002/humu.1380010504
  • [8] THE SKIPPING OF CONSTITUTIVE EXONS INVIVO INDUCED BY NONSENSE MUTATIONS
    DIETZ, HC
    VALLE, D
    FRANCOMANO, CA
    KENDZIOR, RJ
    PYERITZ, RE
    CUTTING, GR
    [J]. SCIENCE, 1993, 259 (5095) : 680 - 683
  • [9] MARFAN PHENOTYPE VARIABILITY IN A FAMILY SEGREGATING A MISSENSE MUTATION IN THE EPIDERMAL GROWTH-FACTOR LIKE MOTIF OF THE FIBRILLIN GENE
    DIETZ, HC
    PYERITZ, RE
    PUFFENBERGER, EG
    KENDZIOR, RJ
    CORSON, GM
    MASLEN, CL
    SAKAI, LY
    FRANCOMANO, CA
    CUTTING, GR
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1992, 89 (05) : 1674 - 1680
  • [10] 4 NOVEL FBN1 MUTATIONS - SIGNIFICANCE FOR MUTANT TRANSCRIPT LEVEL AND EGF-LIKE DOMAIN CALCIUM-BINDING IN THE PATHOGENESIS OF MARFAN-SYNDROME
    DIETZ, HC
    MCINTOSH, I
    SAKAI, LY
    CORSON, GM
    CHALBERG, SC
    PYERITZ, RE
    FRANCOMANO, CA
    [J]. GENOMICS, 1993, 17 (02) : 468 - 475