Transthyretin interacts with metallothionein 2

Area of Science:

• Biochemistry
• Neuroscience
• Protein Interactions

Background:

• Transthyretin (TTR) is a transport protein involved in thyroxine and retinol transport.
• TTR is synthesized in the choroid plexus (CP) for cerebrospinal fluid and by the liver for systemic circulation.
• TTR is implicated in amyloid diseases and amyloid beta peptide (Abeta) sequestration.

Purpose of the Study:

• To explore novel biological roles of TTR through protein-protein interactions.
• To identify potential binding partners of TTR using the yeast two-hybrid system.

Main Methods:

• Yeast two-hybrid system for initial screening.
• Competition binding assays, co-immunoprecipitation, cross-linking, and Western blotting for interaction confirmation.
• Immunofluorescence and dot blot immunoassays for localization and presence in cerebrospinal fluid (CSF).

Main Results:

• A novel interaction between transthyretin (TTR) and metallothionein 2 (MT2) was identified in human liver.
• The interaction was confirmed using multiple biochemical and biophysical methods.
• TTR-MT1/2 complexes were detected in rat choroid plexus, kidney, and cerebrospinal fluid (CSF), with MT1/2 found in the endoplasmic reticulum.

Conclusions:

• Transthyretin (TTR) interacts with metallothionein 1/2 (MT1/2).
• TTR-MT1/2 complexes may have functional significance in normal physiology and in Alzheimer disease pathogenesis.
• These complexes represent a potential novel therapeutic target for Alzheimer disease.