Figures & data
Figure 1 Nedd4-2 ubiquitinates voltage-gated ion channels.
Notes: Nedd4-2 binds to voltage-gated channels in different ways (PY motifs, other motifs, adaptor proteins with PY motifs, etc) to ubiquitinate and sends them for degradation in response to different stimuli. Mutations in channels affecting Nedd4-2 function accumulate channels at the cell surface, causing different pathologies.
Abbreviation: VGIC, voltage-gated ion channel.
Abbreviation: VGIC, voltage-gated ion channel.
Figure 2 The human Nedd4 family of E3 ubiquitin ligases.
Notes: All Nedd4 protein members are composed of an amino-terminal C2 domain (blue), which is involved in lipid membrane binding, and as a protein–protein interaction domain, several WW domains (green), which are involved in the interaction with substrates and other proteins, and a carboxy-terminal HECT domain (orange), which is responsible for the catalytic activity.
Abbreviations: HECT, Homologous to E6AP Carboxy Terminus; Nedd4, Neural precursor cell-Expressed Developmentally Down-regulated 4.
Abbreviations: HECT, Homologous to E6AP Carboxy Terminus; Nedd4, Neural precursor cell-Expressed Developmentally Down-regulated 4.
Table 1 Voltage-gated ion channels regulated by Nedd4-2
Figure 3 Nedd4-2 activity and binding to substrates can be regulated in several ways.
Notes: (A) Regulation of Nedd4-2 by intramolecular interactions. The binding of the WW domain to the endogenous PY motif inhibits Nedd4-2 activity. (B) Nedd4-2 phosphorylation by SGKs and Akt allows the binding of 14-3-3 proteins, inhibiting Nedd4-2 activity. (C) Nedd4-2 can interact with deubiquitinases that can deubiquitinate different substrates. (D) The binding of Ndfip protein adaptors regulates Nedd4-2 activity. (E) AMPK increases Nedd4-2 activity on its substrates.
Abbreviation: AMPK, adenosine 5′-monophosphate (AMP)-activated protein kinase; SGKs, serum and glucocorticoid kinases.
Abbreviation: AMPK, adenosine 5′-monophosphate (AMP)-activated protein kinase; SGKs, serum and glucocorticoid kinases.
