BACKGROUND AND AIMS: Proper organization of synaptic connections is important for the transmission of information in the central and peripheral nervous systems (CNS and PNS). Synaptic remodeling is a process whereby synapses are rewired to form functional neuronal networks. The molecular mechanisms underlying this process are still poorly understood. We have recently identified the scaffold protein Amotl2 as a potential regulator of neuromuscular junction (NMJ) plasticity. Interestingly, many proteins involved in NMJ remodeling are also implicated in the plasticity of synapses in the brain. Therefore, we investigated the expression and function of Amotl2 and closely related proteins Amot and Amotl1, collectively called Angiomotins, in CNS neurons. METHODS: Primary neuronal cultures were prepared from embryonic day 19 rat brains and transfected using Lipofectamine2000 or Amaxa nucleofection. Cells and mouse brain slices were immunostained to visualize Amot, Amotl1 and Amotl2. To assess the function of Amot in CNS, we knocked down its expression in hippocampal neurons using shRNA, and analyzed neuronal morphology using confocal microscopy. RESULTS: All three angiomotins are widely expressed in the brain. In cultured rat hippocampal neurons and mouse brain slices Amotl2 and Amotl1 localize to the synaptic compartment, whereas Amot is distributed in neurites. Amot depletion in neurons leads to reduced dendritic tree arborization and malfunction of the axon initial segment as reflected by aberrant localization of its main components ankyrin G and neurofascin. CONCLUSIONS: Our experiments identify a novel group of proteins that play a critical role in the organization of neurons and may regulate synaptogenesis both in the CNS and PNS. Amot may play a role in dendrite outgrowth and is critical for the establishment of the axon initial segment, suggesting a role in the maintenance of polarity in neurons. This research was supported by the NCN grant 2012/05/E/ NZ3/00487.
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