Androgen regulation of spermatogenesis
C. Yan Cheng in Spermatogenesis, 2018
Claudin 3 is an adhesion protein that is induced by androgen and localizes to newly forming tight junctions at the BTB.4 However, Claudin 3 deficient mice retain fertility, suggesting that other androgen-regulated junctional proteins are sufficient to maintain the BTB.90 Claudin 11 and occludin, major transmembrane components of the BTB, were found to be downregulated in SCARKO mice.3,91,92 The mRNAs encoding Tjp1, Tjp2 iso1, Tjp2 iso2, and Tjp2 iso3 that link the transmembrane tight junction proteins to the cytoskeleton are also downregulated in SCARKO mice, suggesting the possibility that these genes are regulated by testosterone. These results are consistent with the finding that in SCARKO mice the BTB is formed but formation is delayed and the barrier is incomplete.3 Rats injected with flutamide to block AR actions had decreased expression of the Cx43 gap junction mRNA and protein and the loss of Cx43 localization to the BTB, whereas the tight junction associated ZO-1 protein was mislocalized away from the cell surface to the Sertoli cell cytoplasm.93 DHT treatment of hpg mice restored the expression and localization of Claudin 3, Cx-43, and Claudin 11 to the BTB.94
Immune function of epithelial cells
Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald in Principles of Mucosal Immunology, 2020
The structure and function of the tight junctions are established by the transmembrane claudin proteins, a family of 27 genes in mammals, the transmembrane tight junction–associated MARVEL proteins (TAMPs), which include occludin and tricellulin, peripheral membrane scaffolding proteins including zonula occludens-1 and -2, signaling molecules, the cytoskeleton, and the endocytic/vesicular trafficking machinery. The claudins direct assembly of the “molecular gasket” that seals the paracellular space and also define the capacity and charge selectivity of the pore pathway. While occludin and zonula occludens-1 are primarily associated with leak pathway maintenance and regulation, they also play other critical roles. For example, zonula occludens-1 and -2 are required for delivery of claudin proteins to tight junctions, and occludin is capable of regulating the function of some claudin proteins, e.g., claudin-2. Zonula occludens-1 and -2 also bind to and regulate the perijunctional actin filaments that are commonly involved in tight junction barrier regulation. Tight junctions also depend on adherens junctions (the cadherins are the primary component) and desmosomes (the cadherin-like desmoglein and desmocollin proteins are the primary components), both of which are also linked to and regulated by the cytoskeleton (actin and cytokeratin, respectively) but do not form significant barriers to diffusion.
Evaluation Models for Drug Transport Across the Blood–Brain Barrier
Sahab Uddin, Rashid Mamunur in Advances in Neuropharmacology, 2020
TJs and adherence junctions (AJs) mainly constitute the BBB junction complex. TJs are an array of ceaseless intracellular membranous strands or fibrils on the peripheral phase and grooves on endothelial phase. The three integral membrane proteins that form the backbone are claudin, occludin, junction adhesion molecules (JAMs), and numerous cytoplasmic accessory proteins. Claudin 1 and claudin 2 are mainly found in BBB junction, where these proteins interplay with one another to frame a tight seal (Furuse et al., 1998, 1999). Occludin is a regulatory protein with four transmembrane domains. The paracellular barrier of TJ is contributed by the extracellular loop of claudin and occludin originating from the neighboring cells essential for the development of BBB (Hirase et al., 1997; Sonoda et al., 1999). JAMs are immunoglobulin having a single membrane trans-domain. Mainly JAM 1 and JAM 2 are revealed in BBB. They are responsible for cell to cell adhesion, paracellular permeability, and monocyte transmigration (Bazzoni et al., 2000). Major cytoplasmic accessory proteins responsible for the formation of TJs include zonula occludens (ZO) 1, ZO 2, ZO 3, cingulin, and many others. Interaction of transmembrane protein with cytoplasmic protein imposes skeletal rigidity to the endothelial cells (Haskin et al., 1998). Cadherin-Catenin complex and further associated proteins constitute AJ.
The blood–brain and gut–vascular barriers: from the perspective of claudins
Published in Tissue Barriers, 2021
Anna Agata Scalise, Nikolaos Kakogiannos, Federica Zanardi, Fabio Iannelli, Monica Giannotta
The composition of the tight junction components closely correlates with barrier function. Claudins are key components of tight junctions that regulate paracellular permeability. Although much effort has been devoted to an understanding of the structural and functional aspects, and the regulation and physiology of the different members of the claudin family, the question as to how claudins regulate the selective permeability has not been answered yet. Some claudins serve as barriers, while others serve as pores in the epithelium, thus generating the heterogeneity observed in the tightness of the various junctions of diverse tissues. Indeed, endothelial barriers can be more or less stringent, depending on the organ that they protect. The well-studied BBB defends the brain from the entry of serum proteins, inflammatory cells, pathogens and other substances, to thus maintain CNS homeostasis. Less stringent barriers, such as the GVB, still help to avoid dissemination of unwanted molecules throughout the organism.
Congenital alacrima
Published in Orbit, 2022
Zhenyang Zhao, Richard C. Allen
HELIX syndrome is a newly defined disorder characterized by hypohidrosis, electrolyte imbalance, lacrimal gland dysfunction, ichthyosis and xerostomia.34 It is caused by biallelic mutations (autosomal recessive) in CLDN10, which encodes claudin-10, an integral membrane protein essential in the formation of the tight junction plates to maintain cell polarity. Localization of claudin-10 is found along the apical and basolateral membrane in the acinar cells of the exocrine glands, including the salivary and lacrimal glands.65 The mechanistic link between a CLDN10 mutation and alacrima remains elusive but is proposed to be a consequence of losing sodium transport across the tight junction.34 Heat intolerance and alacrima are the earliest signs in these patients and are universally observed in published cases.33,34 Detailed ophthalmic evaluation and description in HELIX patients has yet to be reported.
Is Claudin 4 a Player to Be Reckoned with or Not in the Context of Lung Transplantation?
Published in Journal of Investigative Surgery, 2022
Anna Niroomand, Sandra Lindstedt
PGD that may then follow the IRI is a form of acute lung injury in which edema occurs in both the airspaces and in alveoli. The removal of edema from the air spaces is a critical function of the alveolar barrier but requires intact tight junctions. The endothelial injury that occurs in ischemic injury prior to PGD exacerbates the formation of edema [7]. Alveolar fluid clearance has been associated with increased survival in patients with acute lung injury but has also been associated with pulmonary graft function after transplantation [8]. The alveolar epithelium is a heterogeneous monolayer of cells interconnected by tight junctions at sites of cell-cell contact. Paracellular permeability depends on claudin-family tight junction proteins. The claudin family consists of about 10 to 20 alveolar claudins that are expressed differently throughout the alveolar epithelium.
Related Knowledge Centers
- Cytoplasm
- Epithelium
- Paracellular Transport
- Protein
- Scaffold Protein
- Tight Junction
- Transmembrane Protein
- N-Terminus
- C-Terminus
- Pdz Domain