Publications by authors named "Abraham Tettey-Matey"

Connexins (Cxs) are fundamental in cell-cell communication, functioning as gap junction channels (GJCs) that facilitate solute exchange between adjacent cells and as hemichannels (HCs) that mediate solute exchange between the cytoplasm and the extracellular environment. Mutations in the GJB1 gene, which encodes Cx32, lead to X-linked Charcot-Marie-Tooth type 1 (CMTX1), a rare hereditary demyelinating disorder of the peripheral nervous system (PNS) without an effective cure or treatment. In Schwann cells, Cx32 HCs are thought to play a role in myelination by enhancing intracellular and intercellular Ca signaling, which is crucial for proper PNS myelination.

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Article Synopsis
  • The study identifies TMEM9B, a newly discovered protein that interacts specifically with the endosomal Cl transporters ClC-3 and ClC-4, affecting their activity.
  • Co-expression experiments revealed that TMEM9B significantly reduces the functionality of ClC-3 and ClC-4 in certain cell models, but has minimal impact on other transporters.
  • This research highlights the potential importance of TMEM9B in regulating neuronal endosomal processes and understanding diseases related to these chloride channels.
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Stable cell pools have the advantage of providing a definite, consistent, and reproducible transmission of a transgene of interest, compared to transient expression from a plasmid transfection. Stably expressing a transgene of interest in cells under induction is a powerful way to (switch on and) study a gene function in both in vitro and in vivo assays. Taking advantage of the ability of lentivirus (LV) to promote transgene delivery, and genomic integration and expression in both dividing and nondividing cells, a doxycycline-inducible transfer vector expressing a bicistronic transgene was developed to study the function of connexins in HeLa DH cells.

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  • - ClC-6 and ClC-7 are intracellular proteins that help regulate chloride (Cl) and hydrogen ions (H) in late endosomes and lysosomes, but they function differently, with ClC-7 needing another protein called Ostm1 to operate properly.
  • - Experiments showed that lower levels of external Cl reduce ClC-6 function, while they enhance ClC-7's activity, particularly under acidic conditions or low internal Cl levels.
  • - The study highlighted unique functions and responses of both transporters, indicating that ClC-7's ability to handle Cl may contribute to disease processes like osteopetrosis, emphasizing the need for balanced ion levels in cellular environments.
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  • Endosomes and lysosomes are vital organelles in cells, involved in maintaining protein balance, clearing unwanted materials, and autophagy, all crucial for cell health.
  • Endolysosomes maintain an acidic environment necessary for their function, with voltage-gated Chloride Channels (CLC proteins) playing a key role in regulating pH and chloride levels.
  • Mutations in these CLC proteins can lead to serious conditions like developmental delays and neurodegeneration, with no current cures available, prompting a review of their role in various diseases and the impact of these mutations.
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Connexin (Cx) hemichannels (HCs) are large pore hexameric structures that allow the exchange of ions, metabolites and a variety of other molecules between the cell cytoplasm and extracellular milieu. HC inhibitors are attracting growing interest as drug candidates because deregulated fluxes through HCs have been implicated in a plethora of genetic conditions and other diseases. HC activity has been mainly investigated by electrophysiological methods and/or using HC-permeable dye uptake measurements.

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In this study, we used B16-F10 cells grown in the dorsal skinfold chamber (DSC) preparation that allowed us to gain optical access to the processes triggered by photodynamic therapy (PDT). Partial irradiation of a photosensitized melanoma triggered cell death in non-irradiated tumor cells. Multiphoton intravital microscopy with genetically encoded fluorescence indicators revealed that bystander cell death was mediated by paracrine signaling due to adenosine triphosphate (ATP) release from connexin (Cx) hemichannels (HCs).

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RNA molecules have emerged as a new class of promising therapeutics to expand the range of druggable targets in the genome. In addition to 'canonical' protein-coding mRNAs, the emerging richness of sense and antisense long non-coding RNAs (lncRNAs) provides a new reservoir of molecular tools for RNA-based drugs. LncRNAs are composed of modular structural domains with specific activities involving the recruitment of protein cofactors or directly interacting with nucleic acids.

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Pathogenic mutations in the non-syndromic hearing loss and deafness 1 (DFNB1) locus are the primary cause of monogenic inheritance for prelingual hearing loss. To unravel molecular pathways involved in etiopathology and look for early degeneration biomarkers, we used a system biology approach to analyze Cx30 mice at an early cochlear post-natal developmental stage. These mice are a DFNB1 mouse model with severely reduced expression levels of two connexins in the inner ear, Cx30, and Cx26.

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Prior work supports the hypothesis that ATP release through connexin hemichannels drives spontaneous Ca2+ signaling in non-sensory cells of the greater epithelial ridge (GER) in the developing cochlea; however, direct proof is lacking. To address this issue, we plated cochlear organotypic cultures (COCs) and whole cell-based biosensors with nM ATP sensitivity (ATP-WCBs) at the bottom and top of an ad hoc designed transparent microfluidic chamber, respectively. By performing dual multiphoton Ca2+ imaging, we monitored the propagation of intercellular Ca2+ waves in the GER of COCs and ATP-dependent Ca2+ responses in overlying ATP-WCBs.

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