H/KDEL receptors mediate host cell intoxication by a viral A/B toxin in yeast

Area of Science:

• Microbiology
• Cell Biology
• Toxicology

Background:

• A/B toxins utilize specific cell surface receptors for host cell entry.
• The receptors for some A/B toxins remain unidentified, hindering our understanding of toxin invasion mechanisms.

Purpose of the Study:

• To identify the membrane receptor responsible for the uptake of the K28 toxin in yeast.
• To elucidate the role of the H/KDEL receptor Erd2p in A/B toxin intoxication.

Main Methods:

• Yeast genetics and cell biology techniques were employed.
• Toxin binding assays were performed on wild-type and Erd2p-deficient yeast cells.
• Localization studies of Erd2p and toxin internalization were investigated.

Main Results:

• The yeast H/KDEL receptor Erd2p was identified as the specific receptor for the K28 toxin.
• Erd2p mediates K28 toxin binding to spheroplasts and is essential for in vivo toxicity.
• Erd2p localizes to the plasma membrane, where it binds and internalizes HDEL-tagged cargo, including K28 toxin.

Conclusions:

• Erd2p plays a critical role in K28 toxin cell surface binding and subsequent intoxication.
• H/KDEL receptors at the cell surface may be a common mechanism for A/B toxin entry and intoxication.
• This finding has implications for understanding toxin-host interactions and developing targeted therapies.