An endoplasmic reticulum trafficking signal regulates surface expression of β4 subunit of a voltage- and Ca²⁺-activated K⁺ channel.
Voltage-dependent and calcium-activated K⁺ (MaxiK, BK) channels are widely expressed in many tissues and organs where they play various physiological roles. Here we report discovery of a functional trafficking signal in MaxiK channel accessory β4 subunit that could regulate activity of MaxiK α subunit (hSlo) on the plasma membrane. We demonstrate that β4 is mostly retained within the cell and removal or mutation of β4 trafficking signal significantly enhances its surface expression in HEK293T expression system. In hippocampal slices and cultured neurons we also observed significant β4 expressions within the neurons. Finally, we show that unlike SV1 and β1 subunits, β4 shows no dominant-negative effect on MaxiK channel α subunit. Taken together, we propose β4 subunit of MaxiK channel is mostly retained within the cells without interfering with other subunits. Removal of β4 retention signal increases its surface expression that may lead to reduction of the MaxiK channel activity and neuronal excitability.
Center for Biomedical Studies, University of Texas at Brownsville, Brownsville, TX 78520, USA.
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Cox
South Texas Arthritis Center, Brownsville, TX 78526, USA.
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Toro
Biomedicine Department, University of Texas at Brownsville, Brownsville, TX 78520, USA.
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Pacheco-Otalora
Center for Biomedical Studies, University of Texas at Brownsville, Brownsville, TX 78520, USA; Biomedicine Department, University of Texas at Brownsville, Brownsville, TX 78520, USA.
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Garrido-Sanabria
Center for Biomedical Studies, University of Texas at Brownsville, Brownsville, TX 78520, USA; Biomedicine Department, University of Texas at Brownsville, Brownsville, TX 78520, USA. Electronic address: Masoud.zarei@utb.edu.
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Zarei
D000818:Animals; D002462:Cell Membrane / Q000502:physiology*; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D015870:Gene Expression; D057809:HEK293 Cells; D006624:Hippocampus / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000378:metabolism; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits / Q000235:genetics / Q000378:metabolism*; D008564:Membrane Potentials / Q000502:physiology; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
C494841:KCNMA1 protein, human; C410183:KCNMB4 protein, human; C485821:Kcnmb4 protein, rat; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits; D009419:Nerve Tissue Proteins
Large conductance Ca(2+)-activated K(+); Retention signal; Trafficking signal; β4 subunit