C‐terminal region‐dependent change of antibody‐binding to the Eighth Reelin repeat reflects the signaling activity of Reelin
@article{Kohno2009CterminalRC,
title={C‐terminal region‐dependent change of antibody‐binding to the Eighth Reelin repeat reflects the signaling activity of Reelin},
author={Takao Kohno and Yoshimi Nakano and N Kitoh and Hirokazu Yagi and Koichi Kato and Atsushi Baba and Mitsuharu Hattori},
journal={Journal of Neuroscience Research},
year={2009},
volume={87}
}Reelin is a secreted glycoprotein that plays pivotal roles in the development and function of the brain, but how it activates downstream intracellular signaling is not fully understood. We have recently reported that the highly conserved C‐terminal region (CTR) of Reelin is required for its full signaling activity, although the underlying mechanism remains unknown. During biochemical study of Reelin, we serendipitously found that one commercially available anti‐Reelin antibody G20 can bind to…
19 Citations
Cleavage within Reelin Repeat 3 Regulates the Duration and Range of the Signaling Activity of Reelin Protein*
- BiologyThe Journal of Biological Chemistry
- 2014
It is demonstrated that N-t cleavage of Reelin plays critical roles in regulating the duration and range of Regel functions both in the extracellular milieu and in the intracellular compartments.
Determination of cleavage site of Reelin between its sixth and seventh repeat and contribution of meprin metalloproteases to the cleavage.
- BiologyJournal of biochemistry
- 2016
It is proposed that meprin α and mePRin β join the modulators of Reelin signalling as they cleave Reelin at a specific site and are upregulated under specific pathological conditions.
Functional Importance of Covalent Homodimer of Reelin Protein Linked via Its Central Region*
- Biology, ChemistryThe Journal of Biological Chemistry
- 2011
The results of this study indicate that an intact higher order architecture of reelin multimer maintained by both Cys2101-mediated homodimerization and other non-covalent association present elsewhere in the reelin primary structure are essential for exerting its full biological activity.
Importance of Reelin C-Terminal Region in the Development and Maintenance of the Postnatal Cerebral Cortex and Its Regulation by Specific Proteolysis
- BiologyThe Journal of Neuroscience
- 2015
Results from ectopic expression of mutant Reelin proteins in utero suggest that the dendrite development and maintenance of the MZ require Reelin protein with an intact CTR, indicating that the CTR is necessary for efficient induction of Dab1 phosphorylation in vivo.
Structural Insights into Reelin Function: Present and Future
- Biology, ChemistryFront. Cell. Neurosci.
- 2016
Current findings on the structure of Reelin and its binding to the ApoER2 and VLDLR receptors are discussed, and some areas where proteomics and structural biology can help understanding Reelin function in brain development and human health are discussed.
Regulated Proteolytic Processing of Reelin through Interplay of Tissue Plasminogen Activator (tPA), ADAMTS-4, ADAMTS-5, and Their Modulators
- BiologyPloS one
- 2012
Serine protease tissue plasminogen activator and two matrix metalloproteinases are identified and it is demonstrated that in the murine hippocampus, the expression levels and localization of Reelin proteases largely overlap with that of Reangel, and changes in their protein levels coincided with accelerated Reelin aggregation in a mouse model of AD.
The functions of Reelin in membrane trafficking and cytoskeletal dynamics: implications for neuronal migration, polarization and differentiation.
- BiologyThe Biochemical journal
- 2017
This review addresses and discusses in detail the participation of reelin in the processes underlying neurogenesis, neuronal migration in the cerebral cortex and the hippocampus; and the polarization, differentiation and maturation processes that neurons experiment in order to be functional in the adult brain.
C-Terminal Region Truncation of RELN Disrupts an Interaction with VLDLR, Causing Abnormal Development of the Cerebral Cortex and Hippocampus
- BiologyThe Journal of Neuroscience
- 2017
A new Reln mutant with a truncation of the C-terminal region (CTR) domain shows that Reln mutation can cause abnormal phenotypes in the cortex and hippocampus without cerebellar hypoplasia, and suggests thatreln mutations may cause more subtle forms of human brain malformation than classic lissencephalies.
References
SHOWING 1-10 OF 51 REFERENCES
The extremely conserved C-terminal region of Reelin is not necessary for secretion but is required for efficient activation of downstream signaling
- BiologyNeuroscience Research
- 2007
Structure of a receptor-binding fragment of reelin and mutational analysis reveal a recognition mechanism similar to endocytic receptors
- Biology, ChemistryProceedings of the National Academy of Sciences
- 2007
It is found that both receptor-binding and subsequent Dab1 phosphorylation occur solely in the segment spanning the fifth and sixth reelin repeats (R5–6), which exhibited a suboptimal level of signaling activity and artificial oligomerization resulted in a 10-fold increase in activity, indicating the critical importance of higher-order multimerization in physiological reelin.
Reelin Is a Secreted Glycoprotein Recognized by the CR-50 Monoclonal Antibody
- BiologyThe Journal of Neuroscience
- 1997
It is demonstrated that Reelin is a secreted glycoprotein and that a highly charged C-terminal region is essential for secretion and that an amino acid sequence present in the N- terminal region of Reelin contains an epitope that is recognized by the CR-50 monoclonal antibody.
Reelin molecules assemble together to form a large protein complex, which is inhibited by the function-blocking CR-50 antibody.
- BiologyProceedings of the National Academy of Sciences of the United States of America
- 2000
It is demonstrated that Reelin molecules assemble with each other to form a huge protein complex both in vitro and in vivo, proposing a novel model of the Reelin signaling in neurodevelopment.
Disabled1 Regulates the Intracellular Trafficking of Reelin Receptors*
- BiologyJournal of Biological Chemistry
- 2005
Results indicate that Dab1 regulates both cell surface expression and internalization of Reelin receptors, and these regulations may play a role in correct laminar formation in the developing brain.
Evolutionarily Conserved, Alternative Splicing of Reelin during Brain Development
- BiologyExperimental Neurology
- 1999
Two uncommon, evolutionarily conserved splicing events in the 3' part of the transcript that result in different forms of the reelin protein are identified, suggesting that the corresponding reelin forms are functionally important.
Direct Binding of Reelin to VLDL Receptor and ApoE Receptor 2 Induces Tyrosine Phosphorylation of Disabled-1 and Modulates Tau Phosphorylation
- BiologyNeuron
- 1999
A panel of monoclonal antibodies against reelin, the extracellular matrix protein defective in reeler mutant mice
- BiologyJournal of Neuroscience Methods
- 1998
Reduction of Crk and CrkL expression blocks reelin-induced dendritogenesis
- BiologyJournal of Cell Science
- 2008
It is shown that the inactivation of a conditional Dab1 allele reduces process complexity in correctly positioned neurons in the CA1 region of the mouse hippocampus after birth, and demonstrates that the Crk family proteins are important downstream components of the reelin signaling pathway in the regulation of postnatal hippocampal dendritogenesis.