Post-translational modifications of transporters

Area of Science:

• Biochemistry
• Molecular Biology
• Pharmacology

Background:

• Drug transporters, including solute carrier (SLC) and ATP-binding cassette (ABC) transporters, are crucial for distributing endogenous compounds and xenobiotics.
• These membrane proteins exhibit dynamic structures and conformations during substrate translocation.
• While substrate specificity and structure-function relationships are well-studied, regulatory mechanisms governing their functional expression are less understood.

Purpose of the Study:

• To review the significant role of post-translational modifications in the dynamic regulation of SLC and ABC drug transporters.
• To highlight recent advancements in understanding how these modifications impact transporter structure, function, and regulation.

Main Methods:

• Literature review focusing on post-translational modifications of drug transporters.
• Analysis of molecular mechanisms underlying functional expression modulation.
• Synthesis of current knowledge on transporter regulation.

Main Results:

• Post-translational modifications, such as phosphorylation, ubiquitination, glycosylation, and palmitoylation, significantly modulate drug transporter functional expression.
• These modifications involve covalent additions to amino acid residues, often triggered by signaling cascades.
• The reversibility of these modifications depends on the specific type and signaling context.

Conclusions:

• Post-translational modifications are critical regulators of drug transporter (SLC and ABC) function and expression.
• Further research into these modifications is essential for a comprehensive understanding of transporter dynamics and their physiological/pharmacological roles.