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Intracellular Signaling Affects Focal Adhesions01:17

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Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
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The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
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Anchoring Junctions01:03

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Anchoring junctions are multiprotein complexes that help cells connect to other cells and the extracellular matrix. Anchoring junctions are present on the lateral and basal surfaces of cells, providing strong and flexible connections. Focal adhesions are often formed due to cell interactions with the ECM substrata, which initiate signal transduction via kinase cascades and other mechanisms. Together, they provide stability and tissue integrity. There are three types of anchoring junctions:...
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  11. Paxillin Regulates Androgen Receptor Expression Associated With Granulosa Cell Focal Adhesions

Paxillin regulates androgen receptor expression associated with granulosa cell focal adhesions

Adelaide E Weidner1, Anna Roy1, Kenji Vann1

  • 1Division of Endocrinology, Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA.

Molecular Human Reproduction
|May 8, 2024

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View abstract on PubMed

Summary
This summary is machine-generated.

Paxillin protein reduces androgen receptor levels in granulosa cells, potentially offering protection against androgen excess disorders like PCOS.

Area of Science:

  • Cell Biology
  • Endocrinology
  • Reproductive Biology

Background:

  • Paxillin is an adaptor protein involved in cell adhesion and motility.
  • Paxillin mediates non-genomic androgen receptor (AR) signaling.
  • The role of paxillin in granulosa cells (GCs) is understudied, despite the importance of androgens and apoptosis in these cells.

Purpose of the Study:

  • To investigate the relationship between paxillin and AR in GCs.
  • To determine the effect of paxillin on AR protein stability and localization.
  • To assess the physiological significance of paxillin in a mouse model of polycystic ovary syndrome (PCOS).

Main Methods:

  • Paxillin knockdown in human KGN cells and knockout in mouse primary GCs.
  • AR protein and mRNA half-life measurements.
Keywords:
PCOSandrogen receptorfocal adhesiongranulosa

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  • Co-immunofluorescence and proximity ligation assays.
  • GC-specific paxillin knockout in a DHT-induced PCOS mouse model.

    • Main Results:

    • Paxillin deficiency reduced AR protein levels but not mRNA in GCs.
    • AR protein and mRNA half-lives were decreased in the absence of paxillin.
    • Paxillin and AR co-localize at the plasma membrane in a focal adhesion kinase-dependent manner.
    • Paxillin knockout in mice partially protected against DHT-induced PCOS symptoms and increased estradiol production.

    Conclusions:

    • Paxillin recruits AR to the GC membrane, potentially protecting it from degradation and enabling non-genomic signaling.
    • Paxillin deletion may offer partial protection against androgen excess by reducing AR expression.
    • Paxillin represents a potential therapeutic target for managing androgen-related disorders like PCOS.
    ovary
    paxillin
    polycystic ovary syndrome