Activity dependent regulation of Angiomotin modulates dendritic complexity in hippocampal neurons

Neuronal activity alters synaptic protein composition, which is important for maintaining dendritic complexity. Multiple signaling networks have been implicated in these processes, but how increased neuronal activity regulates their expression remains incompletely understood. The long isoform of Angiomotin, AMOT-130, is a scaffolding protein that recruits signaling proteins involved in regulating cell morphology and has been implicated in dendritic spine morphogenesis during early development. Here, we show that RNAi-mediated depletion of AMOT-130 reduces dendritic arbor complexity in neurons as early as DIV9. Elevated neuronal activity similarly decreases dendritic complexity which is accompanied by reduced AMOT-130 levels. Overexpression of AMOT-130 counteracts this morphological effect, suggesting that its activity-dependent downregulation contributes to dendritic remodelling during early development. We further, demonstrate that elevated neuronal activity promotes ubiquitin-mediated proteasomal degradation of AMOT-130, identifying a mechanism regulating its abundance in developing neurons. These findings suggest that maintaining sufficient AMOT-130 protein levels is necessary for normal dendritic arborization.