The Reelin Receptor ApoER2 Recruits JNK-interacting Proteins-1 and -2

doi:10.1074/jbc.M004119200

The Reelin Receptor ApoER2 Recruits JNK-interacting Proteins-1 and -2*

From the ^‡The Institute of Medical Biochemistry, Department of Molecular Genetics, Biocenter and University of Vienna, A-1030 Vienna, Austria and ^§The Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9046

Abstract

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.

Footnotes

↵* This work was supported by the Austrian Science Foundation Grants F0606 and P13931 (to J. N.) and P11694 and P13940 (to W. J. S).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
↵¶ To whom correspondence should be addressed: Dept. of Molecular Genetics, Biocenter and University of Vienna, Dr. Bohrgasse 9/II, A-1030 Vienna, Austria. Tel.: 43-1-4277-61808; Fax: 43-1-4277-9618; E-mail: JNIMPF@mol.univie.ac.at.
Published, JBC Papers in Press, May 25, 2000, DOI 10.1074/jbc.M004119200
Abbreviations:

LDL

low density lipoprotein

LDLR

low density lipoprotein receptor

VLDLR

very low density lipoprotein receptor

SH3

Src homology 3

ApoER2

apolipoprotein E receptor 2

Dab1

disabled-1

CNR

cadherin-related neuronal receptor

JNK

c-Jun NH₂-terminal kinase

JIP

JNK interacting protein

IB1

islet-brain-1

PCR

polymerase chain reaction

HA

hemagglutinin

GST

glutathione S-transferase

PID

protein interaction domain

PBS

phosphate-buffered saline
- Received May 15, 2000.
The American Society for Biochemistry and Molecular Biology, Inc.