» Articles » PMID: 21518833

SUMO Modification of Cell Surface Kv2.1 Potassium Channels Regulates the Activity of Rat Hippocampal Neurons

Overview
Journal J Gen Physiol
Specialty Physiology
Date 2011 Apr 27
PMID 21518833
Citations 73
Authors
Affiliations
Soon will be listed here.
Abstract

Voltage-gated Kv2.1 potassium channels are important in the brain for determining activity-dependent excitability. Small ubiquitin-like modifier proteins (SUMOs) regulate function through reversible, enzyme-mediated conjugation to target lysine(s). Here, sumoylation of Kv2.1 in hippocampal neurons is shown to regulate firing by shifting the half-maximal activation voltage (V(1/2)) of channels up to 35 mV. Native SUMO and Kv2.1 are shown to interact within and outside channel clusters at the neuronal surface. Studies of single, heterologously expressed Kv2.1 channels show that only K470 is sumoylated. The channels have four subunits, but no more than two non-adjacent subunits carry SUMO concurrently. SUMO on one site shifts V(1/2) by 15 mV, whereas sumoylation of two sites produces a full response. Thus, the SUMO pathway regulates neuronal excitability via Kv2.1 in a direct and graded manner.

Citing Articles

SUMOylation and DeSUMOylation: Tug of War of Pain Signaling.

Calderon-Rivera A, Gomez K, Rodriguez-Palma E, Khanna R Mol Neurobiol. 2024; 62(3):3305-3321.

PMID: 39276308 DOI: 10.1007/s12035-024-04478-w.


Disrupting PIAS3-mediated SUMOylation of MLK3 ameliorates poststroke neuronal damage and deficits in cognitive and sensorimotor behaviors.

Jiang Y, Hu L, Wang B, Zhang B, Shao M, Meng L Cell Mol Life Sci. 2024; 81(1):119.

PMID: 38456949 PMC: 10924033. DOI: 10.1007/s00018-024-05166-7.


Targeted transcriptional upregulation of SENP1 by CRISPR activation enhances deSUMOylation pathways to elicit antinociception in the spinal nerve ligation model of neuropathic pain.

Gomez K, Allen H, Duran P, Loya-Lopez S, Calderon-Rivera A, Moutal A Pain. 2023; 165(4):866-883.

PMID: 37862053 PMC: 11389604. DOI: 10.1097/j.pain.0000000000003080.


SUMOylation of Na1.2 channels regulates the velocity of backpropagating action potentials in cortical pyramidal neurons.

Kotler O, Khrapunsky Y, Shvartsman A, Dai H, Plant L, Goldstein S Elife. 2023; 12.

PMID: 36794908 PMC: 10014073. DOI: 10.7554/eLife.81463.


Hypoxia inhibits the cardiac current through SUMO targeting Kir2.1 activation by PIP.

Xu Y, Yang Y, Chandrashekar A, Gada K, Masotti M, Baggetta A iScience. 2022; 25(9):104969.

PMID: 36060074 PMC: 9437851. DOI: 10.1016/j.isci.2022.104969.


References
1.
Shen L, Tatham M, Dong C, Zagorska A, Naismith J, Hay R . SUMO protease SENP1 induces isomerization of the scissile peptide bond. Nat Struct Mol Biol. 2006; 13(12):1069-77. PMC: 3326531. DOI: 10.1038/nsmb1172. View

2.
Rajan S, Plant L, Rabin M, Butler M, Goldstein S . Sumoylation silences the plasma membrane leak K+ channel K2P1. Cell. 2005; 121(1):37-47. DOI: 10.1016/j.cell.2005.01.019. View

3.
Benson M, Li Q, Kieckhafer K, Dudek D, Whorton M, Sunahara R . SUMO modification regulates inactivation of the voltage-gated potassium channel Kv1.5. Proc Natl Acad Sci U S A. 2007; 104(6):1805-10. PMC: 1794304. DOI: 10.1073/pnas.0606702104. View

4.
Hay R . SUMO: a history of modification. Mol Cell. 2005; 18(1):1-12. DOI: 10.1016/j.molcel.2005.03.012. View

5.
Talley E, Solorzano G, Lei Q, Kim D, Bayliss D . Cns distribution of members of the two-pore-domain (KCNK) potassium channel family. J Neurosci. 2001; 21(19):7491-505. PMC: 6762917. View