Alterations in SUMOylation of the hyperpolarization-activated cyclic nucleotide-gated ion channel 2 during persistent inflammation.

Background: Unilateral injection of Complete Freund's Adjuvant (CFA) into the intra-plantar surface of the rodent hindpaw elicits chronic inflammation and hyperalgesia in the ipsilateral hindlimb. Mechanisms contributing to this hyperalgesia may act over multiple time courses and can include changes in ion channel expression and post-translational SUMOylation. Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels mediate the hyperpolarization-activated current, I .

SUMOylating Two Distinct Sites on the A-type Potassium Channel, Kv4.2, Increases Surface Expression and Decreases Current Amplitude.

Post-translational conjugation of Small Ubiquitin-like Modifier (SUMO) peptides to lysine (K) residues on target proteins alters their interactions. SUMOylation of a target protein can either promote its interaction with other proteins that possess SUMO binding domains, or it can prevent target protein interactions that normally occur in the absence of SUMOylation. One subclass of voltage-gated potassium channels that mediates an A-type current, I, exists as a ternary complex comprising Kv4 pore-forming subunits, Kv channel interacting proteins (KChIP) and transmembrane dipeptidyl peptidase like proteins (DPPL).

Modulator-Gated, SUMOylation-Mediated, Activity-Dependent Regulation of Ionic Current Densities Contributes to Short-Term Activity Homeostasis.

Neurons operate within defined activity limits, and feedback control mechanisms dynamically tune ionic currents to maintain this optimal range. This study describes a novel, rapid feedback mechanism that uses SUMOylation to continuously adjust ionic current densities according to changes in activity. Small ubiquitin-like modifier (SUMO) is a peptide that can be post-translationally conjugated to ion channels to influence their surface expression and biophysical properties.

SUMOylation of the Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel 2 Increases Surface Expression and the Maximal Conductance of the Hyperpolarization-Activated Current.

Small Ubiquitin-like Modifier (SUMO) is a ∼10 kDa peptide that can be post-translationally added to a lysine (K) on a target protein to facilitate protein-protein interactions. Recent studies have found that SUMOylation can be regulated in an activity-dependent manner and that ion channel SUMOylation can alter the biophysical properties and surface expression of the channel. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channel surface expression can be regulated in an activity-dependent manner through unknown processes.