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Ror1-Ror2 complexes modulate synapse formation in hippocampal neurons
S Paganoni1, J Bernstein, A Ferreira
1Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Abstract:
Ror1 and Ror2, a small family of tyrosine kinase receptors, have been implicated in multiple aspects of brain development in C. elegans and X. laevis. More recently, we have shown that these receptors modulate the rate of neurite elongation in cultured rat hippocampal neurons. However, no information is available regarding a potential role of these receptors in other developmental milestones in mammalian central neurons. Neither is the identity known of the Ror ligand(s) and/or the signal transduction pathway(s) in which they participate. Here we report that the down regulation of either Ror1 or Ror2 led to a significant decrease in synapse formation in cultured hippocampal neurons. Simultaneous targeting of Ror proteins, however, did not result in an additive phenotype. Our results also indicated that Ror1 and Ror2 physically interact in the mouse brain, suggesting that they might function as heterodimers in central neurons. In addition, these Ror complexes interacted with Wnt-5a mediating its effects on synaptogenesis. Together, these data suggest that Ror proteins play a key role in Wnt-5a-activated signaling pathways leading to synapse formation in the mammalian CNS.
Insights
Ror1 and Ror2 proteins are crucial for synapse formation in mammalian brain development. These receptors interact with Wnt-5a to regulate synaptogenesis in the central nervous system.
Area of Science:
- Neuroscience
- Molecular Biology
- Developmental Biology
Background:
- Ror1 and Ror2 tyrosine kinase receptors are involved in brain development in model organisms.
- Previous studies showed their role in neurite elongation in rat hippocampal neurons.
- Their function in mammalian central neuron development and associated signaling pathways remains unclear.
Purpose of the Study:
- To investigate the role of Ror1 and Ror2 in synapse formation in mammalian central neurons.
- To identify the ligands and signal transduction pathways involving Ror proteins.
- To elucidate the function of Ror proteins in mammalian central nervous system development.
Main Methods:
- Down-regulation of Ror1 or Ror2 in cultured hippocampal neurons.
- Analysis of synapse formation following Ror protein manipulation.
- Investigation of Ror1 and Ror2 interactions in mouse brain tissue.
- Assessment of Ror complex interaction with Wnt-5a.
Main Results:
- Down-regulating Ror1 or Ror2 significantly decreased synapse formation.
- Simultaneous targeting of Ror1 and Ror2 did not produce an additive effect.
- Ror1 and Ror2 were found to physically interact in the mouse brain, suggesting heterodimer formation.
- Ror complexes interacted with Wnt-5a, mediating its effects on synaptogenesis.
Conclusions:
- Ror1 and Ror2 play a critical role in synapse formation in the mammalian central nervous system.
- Ror proteins function as heterodimers and are integral to Wnt-5a signaling pathways.
- These findings highlight the importance of Ror proteins in Wnt-5a-mediated synaptogenesis in the CNS.
