Cadherin Dynamics in Membrane Trafficking and Disease Mechanisms

Cadherins are essential adhesion molecules that support tissue structure and regulate communication between neighboring cells. Their activity depends on correct movement through membrane trafficking pathways. These pathways include endocytosis, recycling, and targeted delivery to the plasma membrane. When these steps work in balance, cadherins maintain stable junctions and preserve epithelial integrity.

Cadherin trafficking is controlled by small GTPases, adaptor proteins, and cytoskeletal elements. Each group directs cadherins through distinct organelles. Early endosomes decide if cadherins return to the surface or proceed toward degradation. The Golgi network supports maturation and targeted delivery. Lysosomes remove damaged or misfolded cadherin pools. Any disruption in these systems changes how cells adhere and respond to their environment.

Cadherin biogenesis is also shaped by ER-to-Golgi transport and stringent quality-control mechanisms that ensure proper folding and export. Within the Golgi, cadherins undergo critical N-glycosylation and O-glycosylation modifications that determine their surface stability and adhesive strength. Defects in ER–Golgi trafficking, glycan processing, or plasma-membrane delivery can severely impair cadherin function, contributing to cancer progression and developmental disorders.

Improper cadherin trafficking is linked to several diseases. Many cancers show rapid cadherin internalization and reduced surface expression. This loss weakens cell junctions and promotes invasion. Abnormal trafficking in gastric, breast, and colorectal cancers also alters downstream signaling. Neurodevelopmental disorders show changes in cadherin transport that disturb synapse formation and neuronal communication. Inflammatory diseases often accelerate cadherin turnover, which increases barrier leakage and tissue injury.

Organelle dynamics also shift during disease. Endosomes enlarge when cadherin recycling fails. The Golgi becomes fragmented when trafficking stress increases. These structural changes amplify cellular dysfunction. They also modify pathways that regulate growth, polarity, and mechanical stability.

Understanding how cadherins move through membrane systems is important for identifying new therapeutic strategies. This Research Topic welcomes studies that connect membrane trafficking with disease models and mechanistic insights.

Key areas of interest include but are not limited to:
• Cadherin endocytosis and its dysregulation in disease
• Recycling defects that reduce cadherin surface expression
• Golgi and endosomal stress contributing to junction instability
• Trafficking alterations driving cancer progression and metastasis
• Transport defects affecting cadherin function in neurodevelopmental disorders
• Accelerated cadherin turnover during inflammation and barrier disruption
• Therapeutic strategies targeting cadherin transport pathways
• ER-to-Golgi transport defects and quality-control failures that impair cadherin export

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This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
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Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Technology and Code

Keywords: Cadherin trafficking, cell adhesion, endosomal dynamics, disease mechanisms, epithelial integrity

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