The reelin receptor ApoER2 recruits JNK-interacting proteins-1 and -2.
Correct positioning of neurons during embryonic development of the brain depends, among other processes, on the proper transmission of the reelin signal into the migrating cells via the interplay of its receptors with cytoplasmic signal transducers. Cellular components of this signaling pathway characterized to date are cell surface receptors for reelin like apolipoprotein E receptor 2 (ApoER2), very low density lipoprotein receptor (VLDLR), and cadherin-related neuronal receptors, and intracellular components like Disabled-1 and the nonreceptor tyrosine kinase Fyn, which bind to the intracellular domains of the ApoER2 and VLDL receptor or of cadherin-related neuronal receptors, respectively. Here we show that ApoER2, but not VLDLR, also binds the family of JNK-interacting proteins (JIPs), which act as molecular scaffolds for the JNK-signaling pathway. The ApoER2 binding domain on JIP-2 does not overlap with the binding sites for MLK3, MKK7, and JNK. These results suggest that ApoER2 is able to assemble a multiprotein complex containing Disabled-1 and JIPs, together with their binding partners, to the cell surface of neurons. This complex might participate in ApoER2-specific reelin signaling and thus would explain the different phenotype of mice lacking the ApoER2 from that of VLDLR-deficient mice.
Stockinger
W
W
The Institute of Medical Biochemistry, Department of Molecular Genetics, Biocenter and University of Vienna, Austria.
Brandes
C
C
Fasching
D
D
Hermann
M
M
Gotthardt
M
M
Herz
J
J
Schneider
W J
WJ
Nimpf
J
J
D048868:Adaptor Proteins, Signal Transducing; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D003593:Cytoplasm / Q000737:chemistry; D018076:DNA, Complementary / Q000378:metabolism; D004822:Epididymis / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D026502:LDL-Receptor Related Proteins; D008297:Male; D051379:Mice; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000166:cytology; D011392:Proline / Q000378:metabolism*; D011485:Protein Binding; D018110:Receptors, Lipoprotein / Q000378:metabolism*; D000091042:Reelin Protein; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D012697:Serine Endopeptidases; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism; D014018:Tissue Distribution; D020798:Two-Hybrid System Techniques
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D015816:Cell Adhesion Molecules, Neuronal; D018076:DNA, Complementary; D016326:Extracellular Matrix Proteins; D026502:LDL-Receptor Related Proteins; C490666:MAPK8IP1 protein, human; C408376:MAPK8IP2 protein, human; C490665:Mapk8ip protein, mouse; C486564:Mapk8ip2 protein, mouse; D009419:Nerve Tissue Proteins; D018110:Receptors, Lipoprotein; D000091042:Reelin Protein; C098773:low density lipoprotein receptor-related protein 8; D011392:Proline; D005982:Glutathione Transferase; C000717127:RELN protein, human; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases