Nuclear envelope-associated endosomes deliver surface proteins to the nucleus

Area of Science:

• Cell biology
• Molecular biology
• Protein trafficking

Background:

• Endocytosis internalizes molecules via distinct routes: recycling, Golgi transport, or degradation.
• Pseudomonas exotoxin A (PE) typically enters the cytosol via the Golgi and endoplasmic reticulum.

Purpose of the Study:

• To investigate the intracellular trafficking route of Pseudomonas exotoxin A (PE).
• To identify novel endosomal pathways involved in protein internalization and nuclear import.

Main Methods:

• Utilized electron microscopy to visualize internalized PE.
• Employed protein trapping assays to confirm nuclear entry.
• Conducted RNA interference (RNAi) screening to identify key proteins involved in the pathway.

Main Results:

• A significant portion of internalized PE localizes to nuclear envelope-associated endosomes (NAE).
• NAE facilitate the transfer of PE into the nucleoplasm.
• NAE-mediated transfer requires nuclear proteins SUN1 and SUN2, and the Sec61 translocon complex.

Conclusions:

• Identified a novel endosomal route for transporting extracellular proteins to the nucleus.
• Demonstrated that NAE mediate the import of PE into the nucleoplasm.
• Highlighted the role of SUN1, SUN2, and the Sec61 translocon in this nuclear import pathway.