Nectin-1 Binds and Signals through the Fibroblast Growth Factor Receptor

被引：30

作者：

Bojesen, Kirsten B. ^{[1
]}

Clausen, Ole ^{[1
,2
]}

Rohde, Kristian ^{[1
]}

Christensen, Claus ^{[1
]}

Zhang, Lanjun ^{[1
]}

Li, Shizhong ^{[1
]}

Kohler, Lene ^{[1
]}

Nielbo, Steen ^{[2
]}

Nielsen, Janne ^{[1
]}

Gjorlund, Michelle D. ^{[1
]}

Poulsen, Flemming M. ^{[2
]}

Bock, Elisabeth ^{[1
]}

Berezin, Vladimir ^{[1
]}

机构：

[1] Univ Copenhagen, Panum Inst, Dept Neurosci & Pharmacol, Prot Lab, DK-2200 Copenhagen, Denmark

[2] Univ Copenhagen, Dept Biol, SBiN Lab, DK-2200 Copenhagen, Denmark

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2012年 / 287卷 / 44期

关键词：

CELL-ADHESION MOLECULES; FGF-RECEPTOR; NEURITE OUTGROWTH; V-DOMAIN; AFADIN; IMMUNOGLOBULIN; EXPRESSION; INTERACTS; CADHERIN; FAMILY;

D O I：

10.1074/jbc.M112.345215

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Nectins belong to a family of immunoglobulin (Ig)-like celladhesion molecules comprising four members, nectin-1 through nectin-4. Nectins are involved in formation of the mechanical adhesive puncta adherentia junctions of synapses. Nectins share the same overall structural topology with an extracellular region containing three Ig modules, a transmembrane region, and a cytoplasmic region. In nectin-1, the first and second Ig module in the extracellular region are necessary for the trans-interaction with nectin-3 and formation of cis-dimers, respectively. The function of the third Ig module of nectin-1 remains unknown. We here report the structure in solution of the third, membrane-proximal Ig module of mouse nectin-1 (nectin-1 Ig3) solved by means of nuclear magnetic resonance (NMR) spectroscopy. It belongs to the C1 set of the Ig superfamily. Nectin-1 Ig3 was produced as a recombinant protein and induced neurite outgrowth in primary cultures of hippocampal and cerebellar granule neurons, an effect abolished by treatment with the fibroblast growth factor receptor (FGFR) inhibitor SU5402, or by transfection with a dominant-negative FGFR1 construct. We showed by surface plasmon resonance (SPR) analysis that nectin-1 Ig3 directly interacted with various isoforms of FGFR. Nectin-1 Ig3 induced phosphorylation of FGFR1c in the same manner as the whole nectin-1 ectodomain, and promoted survival of cerebellar granule neurons induced to undergo apoptosis. Finally, we constructed a peptide, nectide, by employing in silico modeling of various FGFR ligand-binding sites. Nectide mimicked all the effects of nectin-1 Ig3. We suggest that FGFR is a downstream signaling partner of nectin-1.

引用

页码：37420 / 37433

页数：14

共 52 条

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