HECT-type E3 ubiquitin ligases in nerve cell development and synapse physiology

The development of neurons is precisely controlled. Nerve cells are born from progenitor cells, migrate to their future target sites, extend dendrites and an axon to form synapses, and thus establish neural networks. All these processes are governed by multiple intracellular signaling cascades, among which ubiquitylation has emerged as a potent regulatory principle that determines protein function and turnover. Dysfunctions of E3 ubiquitin ligases or aberrant ubiquitin signaling contribute to a variety of brain disorders like X-linked mental retardation, schizophrenia, autism or Parkinson's disease. In this review, we summarize recent findings about molecular pathways that involve E3 ligases of the Homologous to E6-AP C-terminus (HECT) family and that control neuritogenesis, neuronal polarity formation, and synaptic transmission.