Trans-endocytosis elicited by nectins transfers cytoplasmic cargo, including infectious material, between cells

Area of Science:

• Cell Biology
• Molecular Biology
• Virology

Background:

• Adherens junction proteins, such as nectins, mediate cell-cell adhesion and signaling.
• Trans-cellular transport mechanisms are crucial for intercellular communication and material exchange.
• Pathogen tropism can be influenced by host cell surface molecules and intercellular transport.

Purpose of the Study:

• To investigate the mechanism by which cells expressing nectin-1 interact with nectin-4 on adjacent cells.
• To determine if cytoplasmic cargo can be transferred between cells via this interaction.
• To explore the functional implications of this transfer process, particularly for viral infection.

Main Methods:

• Utilizing cell culture systems expressing nectin-1 and nectin-4.
• Employing trans-endocytosis assays with fluorescently labeled cargo.
• Investigating the role of nectin cytoplasmic tails through deletion and exchange experiments.
• Assessing the infectivity of measles virus (MeV) following intercellular transfer.

Main Results:

• Cells expressing nectin-1 capture nectin-4-containing membranes from adjacent cells through trans-endocytosis.
• Internalized nectin-1/nectin-4 complexes are trafficked via the endocytic pathway.
• The nectin-1 cytoplasmic tail is essential for this transfer process.
• Functional cytoplasmic cargo, including measles virus genomes, can be transferred, leading to infection.

Conclusions:

• A novel process, nectin-elicited cytoplasm transfer (NECT), facilitates the movement of cytoplasmic cargo between cells.
• NECT involves nectin-mediated trans-endocytosis and can transfer functional materials, including infectious viral particles.
• This mechanism may represent a pathway for pathogens to spread and extend their tropism.