Cathartocytosis: Jettisoning of Unwanted Material during Cellular Reprogramming

Area of Science:

• Cell Biology
• Tissue Repair Mechanisms
• Molecular Biology

Background:

• Differentiated cells can reprogram to repair tissue through paligenosis.
• Gastric chief cells reprogram into Spasmolytic-Polypeptide Expressing Metaplasia (SPEM) cells during paligenosis.
• The initial stage of paligenosis involves lysosome-mediated downscaling of mature cell architecture.

Purpose of the Study:

• To investigate the mechanisms of cellular downscaling during paligenosis.
• To identify novel pathways for material ejection from cells during tissue repair.
• To characterize a newly observed lysosome-independent cell cleansing process.

Main Methods:

• Genetic and pharmacological approaches to study cellular processes.
• 3-dimensional light and electron microscopy to visualize cellular structures.
• Analysis of glycoprotein digestion and excretion during paligenosis.

Main Results:

• Sulfated glycoproteins, endoplasmic reticulum membranes, and secretory granule cargo are excreted into the gland lumen during paligenosis.
• This excretion process is mechanistically independent of autophagy.
• A novel cellular mechanism, termed cathartocytosis, involving multi-chambered apical plasma membrane invaginations, was identified for material ejection.
• Cathartocytosis allows rapid ejection of cellular material without lysosomal digestion.

Conclusions:

• Cathartocytosis is a newly described, lysosome-independent mechanism for rapid cellular material ejection.
• This process facilitates cell downscaling during paligenosis and may contribute to pathogen clearance.
• Cathartocytosis represents a distinct pathway for cellular waste management and tissue repair.