Summary

Tight junctions (TJ) are named according to their classical function to seal the cleft between epithelial and endothelial cells against unwanted passage of solutes and water. The main protein families of the TJ are claudins, TJ-associated MARVEL proteins (TAMP, including occludin and tricellulin), junctional adhesion molecules (JAM), and angulins, most of which are connected to the cytoskeleton via adapters such as zonula occludens (ZO) proteins. TJ proteins do not only form barriers but, in contrast, some constitute paracellular ion or water channels. The first molecular structures of claudins and models of TJ channel pores are published. This entry collection aims to provide further insight into the complex machinery of the development and control of tissue formation and cell differentiation.

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Entries
Topic Review
Functions of CD34
CD34 is primarily known as a biomarker for hematopoietic stem cells (HSCs) and hematopoietic stem precursor cells, but it has also been identified as a marker for several non-hematopoietic cells.  All three proteins in the CD34 family share similar structural characteristics, including the presence of serine, threonine, and proline residues in their extracellular domains. These domains are heavily glycosylated and sialylated, which gives the proteins an effective size range of 90–170 kDa and defines the CD34 family as a subfamily of sialomucins.
  • 455
  • 15 May 2023
Topic Review
Zonulin Pathway as a Therapeutic Target
The integrity and thus the function of blood–brain barrier (BBB) TJs play a crucial role in the pathomechanism of neuroinflammatory and neurodegenerative diseases. Previously, it has been suggested that targeting different elements of the zonulin pathway, including actin filaments, TJs, or NF-κB, have potential therapeutic effects on CNS diseases. Indeed, encouraging results are accumulating from a recent preclinical study, using myosin light chain kinase (MLCK) inhibitor ML-7, which attenuates BBB disruption by preventing the disintegration of actin cytoskeletal microfilaments. Similarly, blocking the cleavage of TJ proteins by matrix metalloproteases (MMP) inhibitors, using either direct (broad-spectrum or selective MMP-2 and MMP-9) or indirect inhibitors (COX) has been shown to protect BBB. Peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists, such as rosiglitazone, pioglitazone, or D-allose, also prevented BBB integrity by inhibiting NF-κB activation. Therefore, the use of zonulin inhibitors seems to be justified in the treatment of CNS diseases.
  • 513
  • 04 May 2023
Topic Review
Long Non-Coding RNAs in Triple-Negative Breast Cancer
Triple-negative breast cancer (TNBC) is a more aggressive type of breast cancer due to its heterogeneity and complex molecular mechanisms. TNBC has a high risk for metastasis, and it is difficult to manage clinical conditions of the patients. Long non-coding RNAs (lncRNAs) have emerged as a novel target to treat the multistep process of TNBC. LncRNAs regulate epigenetic expression levels, cell proliferation and apoptosis, and tumour invasiveness and metastasis. Thus, lncRNA-based early diagnosis and treatment options could be helpful, especially for patients with severe TNBC. 
  • 614
  • 20 Apr 2023
Topic Review
RNA-Binding Proteins in Bladder Cancer
RNA-binding proteins (RBPs) are key regulators of transcription and translation, with highly dynamic spatio-temporal regulation. They are usually involved in the regulation of RNA splicing, polyadenylation, and mRNA stability and mediate processes such as mRNA localization and translation, thereby affecting the RNA life cycle and causing the production of abnormal protein phenotypes that lead to tumorigenesis and development. Accumulating evidence supports that RBPs play critical roles in vital life processes, such as bladder cancer initiation, progression, metastasis, and drug resistance.
  • 771
  • 23 Feb 2023
Topic Review
Endocytosis in Health and Disease
Endocytosis is a mechanistic process, associated with internalization of the extracellular materials such as microbes, cellular components, nutrients, or macromolecules. Conventionally, eukaryotic cells use the endocytosis process for the absorption of molecules and secretion of signaling transmitters (hormones and cytokines) to maintain cellular homeostasis. Endocytosis machinery is a well-conserved physiological process in lower to higher organisms, which has been frequently acquired for cellular defense, immune responses, uptake, and energy metabolism. 
  • 895
  • 13 Feb 2023
Topic Review
Isthmin Protein Family
Isthmin (ISM) is a secreted protein family with two members, namely ISM1 and ISM2, both containing a TSR1 domain followed by an AMOP domain. Its broad expression pattern suggests diverse functions in developmental and physiological processes. Multiple studies have focused on the functional analysis of the ISM protein family in several events, including angiogenesis, metabolism, organ homeostasis, immunity, craniofacial development, and cancer.
  • 500
  • 06 Jan 2023
Topic Review
Mitogen-Activated Protein Kinase Signaling Pathway
The basic composition of the mitogen-activated protein kinase (MAPK) pathway is divided into three modules in sequence, with a cascade effect: MAPK kinase kinase (MAPKKK), MAPK kinase (MAPKK), and MAPK. The MAPK signaling pathway is activated in over 50% of human oral cancer cases.
  • 1.5K
  • 11 Oct 2022
Topic Review
Expression, Regulation, and Physiological Relevance of Skin Aquaporins
The skin is the largest organ of the human body, serving as an effective mechanical barrier between the internal milieu and the external environment. The skin is widely considered the first-line defence of the body, with an essential function in rejecting pathogens and preventing mechanical, chemical, and physical damages. Keratinocytes are the predominant cells of the outer skin layer, the epidermis, which acts as a mechanical and water-permeability barrier. The epidermis is a permanently renewed tissue where undifferentiated keratinocytes located at the basal layer proliferate and migrate to the overlying layers. 
  • 743
  • 27 May 2022
Topic Review
Carbohydrate-Binding Modules of Potential Resources
Carbohydrate-binding modules (CBMs) are a class of multi-module enzyme proteins and their function is to respond to bind to the carbohydrate substrate. Cellulose-binding domains (CBDs) are the earliest-discovered CBMs which were used to be catergozied based on their sequence homology. However, with the in-depth study of carbohydrate hydrolases, more modules in carbohydrate-active enzymes were discovered that could bind, in addition to cellulose, to other types of carbohydrates such as chitin, glucan, xylan, or starch. 
  • 931
  • 07 May 2022
Topic Review
Astrocytes as Templates for Angiogenesis
 Angiogenesis is a key process in various physiological conditions in the nervous system and in the retina during postnatal life. Although an increasing number of studies have addressed the role of endothelial cells in this event, the astrocytes contribution in angiogenesis has received less attention.
  • 839
  • 08 Apr 2022
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