Control of Ion Channel Trafficking

Creative Bioarray has developed targeted ubiquitination and deubiquitination methods to help clients achieve control of ion channel trafficking and selective post-translational down-regulation or up-regulation of desired ion channels, providing useful information for the development of powerful therapeutic approaches.

Background

Plasma membrane-localized ion channels sense and respond to changes in the extracellular and intracellular environment and play important roles in a variety of fundamental physiological responses such as neurotransmitter release, muscle contraction, pH, and osmotic regulation. For channels acting on the surface membrane, the whole-cell current (I) is related to the microscopic channel properties by the equation I = N × i × P_o (N is the number of channels in the plasma membrane, i is the unit current, and P_o is the open probability).

Surface density is a major determinant of the complex function of ion channels, and dysregulation of ion channel surface density caused by hereditary or de novo mutations often leads to the development of many serious diseases. Molecules that can correct trafficking defects to control the number of channels in the plasma membrane thus have important physiological and pathological implications. Genetically encoded molecules that can upregulate or downregulate the surface density of ion channels have the potential to serve as research tools and potential therapeutics.

Fig. 1 Principle of controlling ion channel surface density using targeted ubiquitination and deubiquitination with engineered nanobodies. (Morgenstern, 2021)

Our Services

Our research team has developed engineered proteins to help clients selectively and post-translationally modulate the surface density of target ion channels. Our method utilizes single-domain antibodies fused to the catalytic domains of the E3 ubiquitin ligase or a DUB to modulate ion channel surface density to enable selective bidirectional control of their functional expression. We have the strength to provide professional scientific services to our clients, as well as technical consultation and guidance on methods for bidirectional modulation of ion channel surface density using targeted ubiquitination and deubiquitination. Our services include but not limited to:

• Measurement of Ion Channel Surface Density.
  We are dedicated to developing a variety of strategies such as surface biotinylation to provide our clients with the service of measuring or estimating the number of channels on the cell surface.
• Characterization of single-domain antibody binders to ion channel subunits.
  Nanoantibodies that bind to the intracellular domain of the pore-forming subunit of the channel or auxiliary subunit can deliver targeted post-translational modifications to the ion channel of interest. Therefore, we also provide our clients with the separation and characterization services of single-domain antibody binders to selected proteins.
• Regulation of ion channels.
  Our targeted ubiquitination/deubiquitination approach has great potential in studying ion channel function. Based on this method, we can provide service and technical support for our clients in multiple research projects. For example:
• Rescue of a trafficking-deficient KCNQ1 mutant channel by targeted deubiquitination.
• Elimination of surface Ca_V2.2 channels by targeted ubiquitination.

Creative Bioarray has successfully helped clients complete several projects related to the control of ion channel trafficking and accumulated rich experience. If you are interested in our services, please feel free to contact us for more details. We are pleased to communicate with you about your project and optimize the existing solutions to meet your scientific research needs.

Reference

1. Morgenstern, T. J.; Colecraft, H. M. Controlling ion channel trafficking by targeted ubiquitination and deubiquitination//Methods in Enzymology. Academic Press, 2021, 654: 139-167.