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Anatomy and Physiology of Balance
Published in R James A England, Eamon Shamil, Rajeev Mathew, Manohar Bance, Pavol Surda, Jemy Jose, Omar Hilmi, Adam J Donne, Scott-Brown's Essential Otorhinolaryngology, 2022
Nishchay Mehta, Andrew Forge, Jonathan Gale
The apical surface of a hair cell is covered by large, actin-rich, rod-like microvillar projections called stereocilia, grouped in a bundle (the ‘hair bundle’), wherein stereocilia progressively increase in length, like a staircase, with one large microtubule-based true cilium called the kinocilium positioned behind the longest row of stereocilia. The hair bundle staircase and position of the kinocilium define the axis of sensitivity or ‘polarity’ of the hair bundle (note the kinocilium, although present in early embryonic development, is absent in mature cochlear hair cell bundles). The tips of each shorter stereocilium is linked to the shaft of its neighbouring taller stereocilium by a thin proteinaceous filament, the tip link. Tip links are composed of two linear proteins joined end to end: cadherin 23 and protocadherin 15. Defects in one of these proteins are associated with different forms of Usher's syndrome. All of the hair cells in a crista are orientated in a single direction, along the plane of the semicircular duct, whereas hair cells in the maculae are arranged in a multiplanar orientation.
Cell Structure and Functions
Published in Malgorzata Lekka, Cellular Analysis by Atomic Force Microscopy, 2017
In both the extracellular and the cytoplasmic domains, each class of cadherin family possesses its own characteristics [19]. Classical cadherins contain extracellular calcium binding domains, including the histidine-alanine-valine (HAV) and tryptophan (W) conserved motifs, along with cytoplasmic domain that binds to β-catenin and protein p120 and connects the cadherin to the actin cytoskeleton. The most common members of classical cadherins are E-cadherin, which is mostly expressed in epithelial tissue of various organs and recognized as one of the suppressors of cancers, N-cadherin that is mainly found in neural tissue and many cells at their fetal stage of development, but also it is common to many metastatic tumors and therefore known as a tumor inducer, and P-cadherin, usually found initially in the placenta. Another class of the cadherin family are desmosomal cadherins that have similar motifs as classical ones, but instead of one tryptophan, they contain two tryptophan molecules, truncated cadherins that do not have a cytoplasmic domain but, instead of, they use glycosyl-phophatidylinositol (GPI) as an anchor, protocadherins with extracellular domain similar to desmosomal cadherins but with distinct cytoplasmic domains, and fat cadherins that with their cytoplasmic domains interacting with a different set of cytoplasmic proteins.
Positive Selection of B-Cell Repertoire, Idiotype Networks and Immunological Memory
Published in Maurizio Zanetti, J. Donald Capra, The Antibodies, 2002
Maryse Brait, Georgette Vansanten, Annette Van Acker, Carl De Trez, Chantal Masungi Luko, Christian Wuilmart, Oberdan Leo, Robert Miller, Roy Riblet, Jacques Urbain
The complexities and properties of the immune and nervous systems have often been compared. Both systems rest upon a huge number of cells; both are predetermined to predict the imprevisible and both display memory, which represent the adaptation to the internal and external environments. A further analogy can be found in the recent discovery of protocadherins (PCAD). PCAD are made up of V and C exons and contain three classes. In the a class, 15 Va parts, in the p class 15 functional Vp parts and in the 7 class 22 functional V7 parts can be linked to the corresponding C parts. If one assumes homophilic binding, a three-dimensional structure made up of 4950 neurons (15 X 15 X 22) emerges from one stem cell (for a recent review see [102]).
Whole genome sequencing and inheritance-based variant filtering as a tool for unraveling missing heritability in pediatric cancer
Published in Pediatric Hematology and Oncology, 2023
Charlotte Derpoorter, Ruben Van Paemel, Katrien Vandemeulebroecke, Jolien Vanhooren, Bram De Wilde, Geneviève Laureys, Tim Lammens
The candidate variant in FAT4 (rs72914988, NM_001291303.3:c.7358G>T) is located in exon 9/18 (NM_001291303.3) and was confirmed by Sanger sequencing (Figure 3A). Both patients and their related family members (obligate carriers) are heterozygous for the variant, while it is absent in the unrelated parents and grandparents. The population allele frequency is very rare with 0.1170% in ExAC-NFE. Biallelic mutations in FAT4 have been associated with Hennekam lymphangiectasia-lymphedema syndrome 2 (HKLLS2, MIM 616006) and Van Maldergem syndrome 2 (VMLDS2, MIM 615546). The human FAT4 protocadherin is a large protein consisting of 4983 amino acids and composed of a 32 Cadherin repeat, two Calcium-binding EGF domains, a hEGF domain and two Laminin G domains. The candidate variant is located in a cadherin domain (Figure 3B) and was found highly conserved (Figure 3C). The variant introduces an Isoleucine, a bigger and more hydrophobic amino acid as compared to the wild-type Serine (p.Ser2453Ile), which can alter the cell–cell interaction function of the domain.
The Genes Involved in Dentinogenesis
Published in Organogenesis, 2022
Shuang Chen, Han Xie, Shouliang Zhao, Shuai Wang, Xiaoling Wei, Shangfeng Liu
The role of the cell junction in oral development and disease is poorly understood. Occludin (OCLN), claudin-1 (CLDN1), and zonula occludens-1/2 (Zo1/2) play important roles in odontoblast differentiation.114 CNRs, protocadherin (Pcdh)-γ, and Reelin are related to both morphogenesis and cell differentiation events.28 E-cadherin and P-cadherin have differential and specific roles during morphogenesis115 and connexin 43 is expressed in odontoblasts.116 The expression patterns of CLDN1, OCLN, ZO-1, and ZO-2 are different. Tight junctions (TJs) of the rat lower incisor odontoblasts may play an important role in the early differentiation of odontoblasts, especially in determining the direction of mineral secretion and establishing the distal membrane domain.114
Hypoplastic left heart syndrome (HLHS): molecular pathogenesis and emerging drug targets for cardiac repair and regeneration
Published in Expert Opinion on Therapeutic Targets, 2021
Anthony T Bejjani, Neil Wary, Mingxia Gu
Work by Liu et al. suggests a digenic etiology where the combined knockout of Sap130 and Pcdha9 is sufficient to cause HLHS-like phenotypes in mice. They showed that Sap130 is required for cardiomyocyte proliferation, whereas protocadherin 9 (Pcdha9) promotes proper valve formation [18]. It is not surprising to find gene mutations that can cause defective cardiomyocyte proliferation; however, in their digenic model, the combined deletion of Sap130 and Pcdha9 also resulted in a significant proportion of the litter having congenital heart defects (CHDs), as well as ventricular hypoplasia. However, none of the mice developed the multiple phenotypes associated with HLHS. This calls into question the specificity of their animal model for HLHS, but also highlights the necessity of more extensive genetic screening to potentially uncover HLHS-specific mutations. Despite the lack of specificity, this animal model is proof that genetic defects are sufficient to cause complex CHDs. To date, there is no animal model for HLHS, which highlights (1) the complex etiology of HLHS and (2) the necessity to generate animal models to better understand disease onset and progression.