Tissue-Specific Biotinylation for Interorgan Communication.

Area of Science:

• Molecular Biology
• Physiology
• Biochemistry

Background:

• Interorgan communication is crucial for organismal adaptation and function.
• Disruptions in organ signaling networks are linked to various diseases.
• The secreted proteome's role in interorgan signaling is poorly understood due to identification challenges.

Purpose of the Study:

• To present a protocol for identifying and tracing secreted proteins using a novel mouse model.
• To enable the characterization of low-abundance secreted proteins and their origins/destinations.
• To provide new insights into secretory protein networks in development, homeostasis, and disease.

Main Methods:

• Utilized R26 BirA*G3-ER knock-in mice with an engineered biotin ligase.
• Labeled secreted proteins within the endoplasmic reticulum of specific organs.
• Developed methods for enrichment and identification of secreted proteins trafficked to distal organs.

Main Results:

• Successfully enabled the labeling of all secreted proteins within the ER of specific organs.
• Facilitated the identification of low-abundance secreted proteins.
• Allowed for the determination of secreted protein origins and destinations.

Conclusions:

• The R26 BirA*G3-ER mouse model provides a powerful tool for studying interorgan communication.
• This approach enhances the understanding of secretory protein networks.
• Offers new avenues for investigating mechanisms of development, homeostasis, and disease.