The Pafah1b complex interacts with the reelin receptor VLDLR
Guangcheng Zhang1, Amir H Assadi, Robert S McNeil
1The Cain Foundation Laboratories, Texas Children's Hospital, Houston, Texas, United States of America.
Plos One
|March 3, 2007
Summary
The Pafah1b complex interacts with the VLDLR receptor, influencing brain development. This interaction is crucial for proper cortical layer formation, suggesting a key role in Reelin signaling pathways.
Area of Science:
- Neuroscience
- Molecular Biology
- Developmental Biology
Background:
- Reelin signaling is essential for brain development, orchestrating cortical structure formation.
- Reelin activates VLDLR and ApoER2 receptors, leading to Dab1 phosphorylation.
- Lis1 (Pafah1b1) is a component of the Pafah1b complex and interacts with phosphorylated Dab1.
Purpose of the Study:
- To investigate the role of the entire Pafah1b complex in Reelin signaling.
- To determine the involvement of Pafah1b in cortical layer formation.
- To elucidate the specific interactions between Pafah1b subunits and Reelin receptors.
Main Methods:
- Investigated the binding of Pafah1b complex subunits (Pafah1b2, Pafah1b3) to VLDLR and ApoER2.
- Generated and analyzed compound mutant mice (Pafah1b1(+/-);Apoer2(-/-)) and (Pafah1b1(+/-);Vldlr(-/-)).
- Observed forebrain phenotypes, including cortical layer organization and hippocampal structure.
Main Results:
- Pafah1b2 and Pafah1b3 specifically bind to the NPxYL sequence of VLDLR, not ApoER2.
- Pafah1b1(+/-);Apoer2(-/-) mice displayed a reeler-like phenotype with inverted cortical layers and disorganization.
- Pafah1b1(+/-);Vldlr(-/-) double mutants did not exhibit these severe developmental defects.
Conclusions:
- The Pafah1b complex directly interacts with the VLDLR receptor.
- This interaction is critical for Reelin signaling downstream of VLDLR.
- The findings reveal a novel cross-talk mechanism essential for proper brain development and cortical organization.
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