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The melanocyte and melaninogenesis
Published in Dimitris Rigopoulos, Alexander C. Katoulis, Hyperpigmentation, 2017
Dimitrios Xekardakis, Sabine Krueger-Krasagakis, Konstantinos Krasagakis
Several ion channels seem to have specific roles in melaninogenesis. These channels function at the plasma membrane and at the membrane of intracellular organelles of the melanocytes. The three most important ion channels that operate across the plasma membrane and modulate pigmentation are TRPM1, TRPM7, and TRPA1. They all belong to the transient receptor potential (TRP) channel family. TRPM1 levels are associated with basal pigmentation, according to the fact that a reduction of TRPM1 expression leads to decreased cellular melanin content. TRPM1 expression is controlled by MITF. On the other hand, TRPA1 is activated by ultraviolet A (UVA) and contributes to a rapid increase of melanin. The exact role of TRPM7 in melaninogenesis remains unknown. The most important intracellular ion channels are the endolysosomal TRPML channels, which belong to the mucolipin (ML) subfamily of TRP channels and regulate melanosomal function; the TPC (two-pore channels), which are expressed in acidic organelles and are regulators of melanosomal physiology and pigmentation; and the ClC-7 (chloride channels, isoform 7), which affect the melanosomal differentiation. There are also melanosomal-specific ion channel proteins that regulate at various steps the melaninogenesis that takes place in the melanosome. The most important of them are OCA2, SLC45A2, SLC24A5, and the OA1 ATPases.23 Finally, mitochondrial dynamics regulate melaninogenesis by accelerating degradation of MITF, via modulation of the signaling pathway reactive oxygen species (ROS)–ERK.24
Multimodal imaging in Schubert-Bornschein congenital stationary night blindness
Published in Ophthalmic Genetics, 2023
Maurizio Battaglia Parodi, Alessandro Arrigo, Firuzeh Rajabian, Ahmad Mansour, Stefano Mercuri, Vincenzo Starace, Alessandro Bordato, Maria Pia Manitto, Elisabetta Martina, Francesco Bandello
We included three patients suffering of CSNB Schubert-Bornschein subtype, two with cCSNB and one with iCSNB. Genetic analyses revealed that two patients had pathogenic variant on TRPM1 gene, on chromosome 15q: one with the homozygous pathogenic variant c.545-3C>G, p.(?); the other with the pathogenic variants c.1314 G>A, p.(=) and c.54 + 5 G>A, p.(?) (compound heterozygosity). The last patient had the c.3011T>G, p.(Met1004Arg) pathogenic variant on gene CACNA1F, chromosome X. Complete patients’ data are listed in Table 1. All patients were male, with a mean age of 28 + 9.53 SD. Medical history was negative, except for the night blindness since early childhood. Patients had a mean BCVA of 0.24 ± 0.04 LogMAR, whereas healthy subjects had a BCVA of 0.0 ± 0.0 SD LogMAR.
Investigational drugs in early phase clinical trials targeting thermotransient receptor potential (thermoTRP) channels
Published in Expert Opinion on Investigational Drugs, 2020
Asia Fernández-Carvajal, Rosario González-Muñiz, Gregorio Fernández-Ballester, Antonio Ferrer-Montiel
Another important family within the TRP ion channel superfamily is the transient receptor potential melastatin (TRPM) receptors, composed of eight members. They can be subdivided into four groups, based on structural homology: TRPM1 and 3, TRPM4-5, TRPM6-7, and TRPM2 and 8 [55]. Most of these plasma membrane ion channels are nonselective Ca2+-permeable (TRPM1-3 and TRPM6-8), while TRPM4/5 are Ca2+-impermeable. In addition, TRPM6-7 are Mg2+-permeable and involved in mammalian Mg2+ homeostasis [56]. TRPM members are differently expressed in many tissues, including primary sensory neurons (TRPM3, TRPM8), prostate (TRPM8), pancreatic β–cells (TRPM2, TRPM3, TRPM5), retina cells (TRPM1), kidney (TRPM6), liver, and heart (TRPM4), among others [57]. Unlike the other TRP channels, TRPM channels lack the N-terminal ankyrin repeats.
Novel frameshift mutation in NYX gene in a Russian family with complete congenital stationary night blindness
Published in Ophthalmic Genetics, 2019
Marianna E. Ivanova, Inna V. Zolnikova, Ketevan V. Gorgisheli, Dmitry S. Atarshchikov, Preetam Ghosh, Debmalya Barh
The NYX gene (OMIM: 300278) located in the X chromosome (Xp11.4) encodes a small class II leucine-rich repeat (LRR) proteoglycan protein Nyctalopin of 481 amino acid length and is expressed at ganglion cell layer, inner and outer nuclear layers, and retinal photoreceptor-to-ON bipolar cell synapse (12,13). The Nyctalopin is essential in the localization of TRPM1 protein in the retinal depolarizing bipolar cells (DBCs) for normal vision; thus it plays an important role in the retinal ON-pathway (14). Inhibition of Nyctalopin leads to the mislocalization of TRPM1 protein leading to the development of CSNB1A (14,15). The LRR domains of Nyctalopin are critical for its function and mutations in the NYX gene that disrupt the LRR tertiary structure of the Nyctalopin protein disrupt the functions of the protein leading to CSNB1A (16). So far, more than 70 pathogenic variations (micro del/dup and point mutations) in the LRR domains of the NYX gene associated with CSNB1A have been reported in various populations (1). In this report, a novel frameshift mutation (c.283delC, p.His95fs, NM_022567.2) associated with CSNB1A is described for the first time in a Russian family.