Structure and function of thyroid hormone plasma membrane transporters

Area of Science:

• Molecular Biology
• Endocrinology
• Cell Biology

Background:

• Thyroid hormones (TH) are essential for development and metabolism.
• TH are charged amino acid derivatives and cannot freely diffuse across lipid bilayers.
• Transporter proteins are crucial for cellular uptake of TH.

Purpose of the Study:

• To review the current understanding of transmembrane transport of TH.
• To highlight the diversity of TH transmembrane transporters.
• To explain the impact of MCT8 gene mutations on TH transport and human health.

Main Methods:

• Review of existing literature on TH transport mechanisms.
• Analysis of protein-TH interactions, including hydrophobic and polar interactions.
• Utilizing homology modeling to understand MCT8 mutations' effects.

Main Results:

• Monocarboxylate transporter 8 (MCT8, SLC16A2) is identified as a key TH transporter.
• Mutations in the MCT8 gene are linked to psychomotor retardation.
• Proteins bind TH via hydrophobic interactions and specific polar interactions.

Conclusions:

• MCT8 plays a critical role in TH transport and neurological development.
• Understanding TH transporter diversity is essential for comprehending TH regulation.
• MCT8 mutations likely impair protein folding and transport function.