negative regulation of adherens junction organization

Definition

Target type: biologicalprocess

Any process that stops, prevents or reduces the frequency, rate or extent of adherens junction organization. [GO_REF:0000058, GOC:als, GOC:TermGenie, PMID:21724833]

Negative regulation of adherens junction organization is a crucial biological process that involves the modulation and control of the assembly, disassembly, and stability of adherens junctions. Adherens junctions are cell-cell adhesion complexes that play a vital role in maintaining tissue integrity, cell polarity, and morphogenesis. They are primarily composed of transmembrane adhesion proteins, such as cadherins, which interact with their counterparts on adjacent cells, and intracellular adaptor proteins, such as catenins, that link cadherins to the actin cytoskeleton. The negative regulation of this process involves a complex interplay of signaling pathways, molecular interactions, and cellular mechanisms that aim to reduce or inhibit the formation, strengthening, or stability of adherens junctions. Key molecular players involved in this process include:

- **Cadherin phosphorylation:** Phosphorylation of cadherin molecules by kinases, such as Src or tyrosine kinases, can disrupt their interactions with catenins, leading to the destabilization of adherens junctions.

- **Catenin degradation:** The ubiquitination and subsequent proteasomal degradation of catenins, particularly β-catenin, can weaken the connection between cadherins and the actin cytoskeleton, promoting junction disassembly.

- **Rho GTPase signaling:** Rho GTPases, like RhoA and Rac1, are involved in regulating actin dynamics and cytoskeletal rearrangements. RhoA activation can promote the formation of stress fibers and the contraction of the actin cytoskeleton, which can indirectly destabilize adherens junctions. Conversely, Rac1 activation can promote junction assembly.

- **Endocytosis:** Endocytosis of cadherin-catenin complexes can internalize these molecules from the plasma membrane, reducing their availability at the cell surface and weakening adherens junctions.

- **Transcriptional regulation:** Transcription factors, such as Snail, Slug, and Twist, can repress the expression of cadherin genes, leading to a decrease in cadherin protein levels and reduced junction formation.

- **Extracellular matrix interactions:** The composition and organization of the extracellular matrix can influence the formation and stability of adherens junctions. Degradation or remodeling of the extracellular matrix can disrupt these junctions.

The negative regulation of adherens junction organization is essential for various cellular processes, including:

- **Cell migration:** During development and wound healing, cells must break apart from existing junctions to migrate to new locations.

- **Tissue morphogenesis:** The controlled disassembly and reassembly of adherens junctions are required for the proper shaping and organization of tissues.

- **Cellular response to stress:** In response to various stressors, such as mechanical forces or changes in cell density, cells can modulate their adherens junctions to adapt to the new environment.

- **Cancer progression:** Disruption of adherens junction organization can contribute to the invasion and metastasis of cancer cells.

In conclusion, negative regulation of adherens junction organization is a tightly controlled and multifaceted process that involves numerous molecular players and signaling pathways. It plays a critical role in ensuring the proper functioning of tissues, cellular migration, and development, and its dysregulation can contribute to various disease states.'
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Proteins (1)

Compounds (5)