SRGAP2 and Its Human-Specific Paralog Co-Regulate the Development of Excitatory and Inhibitory Synapses
| Autor: | Franck Polleux, Cécile Charrier, Matteo Fossati, Ewoud R.E. Schmidt, David Stroebel, Rocco Pizzarelli, Justine V. Kupferman |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Patch-Clamp Techniques Neurogenesis Synaptogenesis Neural circuitry AMPA receptor Biology Inhibitory postsynaptic potential Synaptic Transmission 03 medical and health sciences Postsynaptic potential Biological neural network Humans Neural networks (Neurobiology) Gephyrin General Neuroscience GTPase-Activating Proteins Excitatory Postsynaptic Potentials Neural Inhibition Receptors GABA-A Excitation (Physiology) 030104 developmental biology Neurology Synapses Synaptic plasticity Excitatory postsynaptic potential biology.protein Neuroscience |
| Zdroj: | Neuron. 91:356-369 |
| ISSN: | 0896-6273 |
| DOI: | 10.1016/j.neuron.2016.06.013 |
| Popis: | The proper function of neural circuits requires spatially and temporally balanced development of excitatory and inhibitory synapses. However, the molecular mechanisms coordinating excitatory and inhibitory synaptogenesis remain unknown. Here we demonstrate that SRGAP2A and its human-specific paralog SRGAP2C co-regulate the development of excitatory and inhibitory synapses in cortical pyramidal neurons in vivo. SRGAP2A promotes synaptic maturation, and ultimately the synaptic accumulation of AMPA and GABAA receptors, by interacting with key components of both excitatory and inhibitory postsynaptic scaffolds, Homer and Gephyrin. Furthermore, SRGAP2A limits the density of both types of synapses via its Rac1-GAP activity. SRGAP2C inhibits all identified functions of SRGAP2A, protracting the maturation and increasing the density of excitatory and inhibitory synapses. Our results uncover a molecular mechanism coordinating critical features of synaptic development and suggest that human-specific duplication of SRGAP2 might have contributed to the emergence of unique traits of human neurons while preserving the excitation/inhibition balance. |
| Databáze: | OpenAIRE |
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