CC BY
11
OM&P
Section MOLECULAR NEUROSCIENCE
References
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2. Schuster S, Rivalan M, Strauss U, Stoenica L, Trimbuch T, Rademacher N, Parthasarathy S, Lajko D, Rosenmund C, Shoichet SA, Winter Y, Tarabykin V, Rosario M. NOMA-GAP/ARHGAP33 regulates synapse development and autistic-like behavior in the mouse. Mol Psychiatry 2015 Sep; 20(9): 1120-1131.
The Suppressors of Cytokine Signalling Socs6 and Socs7 are Essential for Cortical Layering and Reelin Signalling
Anne K. Voss* and Tim Thomas
Walter and Eliza Hall Institute of Medical Research, Melbourne, Parkville, Victoria 3052, Australia.
* Presenting e-mail: [email protected]
Mutations of the reelin gene cause severe defects in cerebral cortex development and profound intellectual impairment. While many aspects of the reelin signalling pathway have been identified, the molecular and ultimate cellular consequences of reelin signalling remain unknown. Specifically, it is unclear if termination of reelin signalling is as important for normal cortical neuron migration as activation of reelin signalling.
Aims
The aim of this project was to determine the role of members of the suppressors of cytokine signalling (SOCS) family of negative regulators of cell signalling in reelin signalling and cortical layer formation.
Methods
The methods used included mice that were single or double deficient for Socs6 and/or Socs7, histological analysis, immunofluorescence, BrdU birth dating, telencephalon explant and cortical neuron migration cultures, protein affinity purification, immunoprecipitation, immunoblotting or mass-spectrometry, isothermal titration calorimetry and functional mutation.
Results
We discovered that combined loss of the suppressors of cytokine signalling, SOCS6 and SOCS7, recapitulated the cortical layer inversion seen in mice lacking reelin and led to a dramatic increase in the reelin signalling molecule disabled (DAB1) in the cortex. The SRC homology domains of SOCS6 and SOCS7 bound DAB1 ex vivo. Mutation DAB1Y300F greatly diminished binding and protected from degradation by SOCS6. Phosphorylated DAB1 was elevated in cortical neurons in the absence of SOCS6 and SOCS7.
Conclusions
We concluded that constitutive activation of reelin signalling was equally detrimental as lack of activation. We hypothesise that by terminating reelin signalling, SOCS6 and SOCS7 may allow new cycles of reelin signalling to occur and that these may be essential for cortical neuron migration.
A Dynamic Unfolded Protein Response Controls Cortical Neurogenesis
Laurent Nguyen*
GIGA-Neurosciences, Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège, Belgium.
* Presenting e-mail: [email protected]
22 Opera Med Physiol 2016 Vol. 2 (S1)
