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Lysosomal Ion Channels and Human Diseases
Published in Tian-Le Xu, Long-Jun Wu, Nonclassical Ion Channels in the Nervous System, 2021
Peng Huang, Mengnan Xu, Yi Wu, Xian-Ping Dong
As a newly identified Ca2+ store (Christensen et al., 2002; Wang et al., 2012), the lysosome in intracellular Ca2+ signaling has attracted attention in recent years. By releasing Ca2+, the lysosome not only activates local Ca2+ signaling events but also, along with the endoplasmic reticulum (ER), modulates global cytosolic Ca2+ signaling events using a mechanism similar to the Ca2+-induced Ca2+ release (CICR). This further causes Ca2+ entry from the extracellular space due to the depletion of the ER Ca2+ store, evoking global Ca2+ signals (Kilpatrick et al., 2013). TRPML1 has been implicated in both local and global Ca2+-dependent signaling pathways. On the one hand, by releasing lysosomal Ca2+, TRPML1 activates local Ca2+-dependent signaling pathways including the aforementioned CaM-mTORC1 signaling pathway (Sun et al., 2018) and calcineurin (CaN)-TFEB signaling pathway (Medina et al., 2015) to adapt to nutrient starvation. On the other hand, TRPML1 can evoke global Ca2+ signals by inducing ER-dependent Ca2+ release, probably through lysosome-ER membrane contact sites. This further induces subsequent Ca2+ entry from the extracellular space due to the ER Ca2+ depletion (Atakpa et al., 2018; Kilpatrick et al., 2013, 2016, 2017; Morgan et al., 2013; Patel and Brailoiu, 2012; Penny et al., 2015). Moreover, new studies have revealed mitochondria-lysosome membrane contact sites (Wong et al., 2018), at which TRPML1 can directly transfer Ca2+ from lysosomes to mitochondria (Peng et al., 2020). Thus, TRPML1 provides an additional mechanism in modulating intracellular Ca2+ dynamics.
Human bronchial-pulmonary proteomics in coronavirus disease 2019 (COVID-19) pandemic: applications and implications
Published in Expert Review of Proteomics, 2021
Heng Wee Tan, Yan-Ming Xu, Andy T. Y. Lau
Interactions between virus and host membrane proteins are crucial for the viral lifecycle. Using BioID proximity labelling technique, St-Germain et al. [97] showed that SARS-CoV-2 proteins predicted with at least one transmembrane domain (spike, envelope, membrane, NSP3, NSP4, NSP6, ORF3A, ORF7A, and ORF7B), along with a few non-membrane-associated but poorly understood proteins (ORF3B, ORF6, ORF8, and ORF9B), were able to interact with a range of host membrane-associated proteins, such as those involved in intracellular vesicle trafficking pathways (e.g. cholesterol and lipid) and endoplasmic reticulum-related membrane contact site (MCS) components. It was proposed that the human MCS lipid transfer system might be an attractive drug target for COVID-19 [97]. Curated data of their work can be found at BioGRID (www.thebiogrid.org) [98], a database that holds over 1.7 million protein, genetic, or chemical interactions obtained from humans and other model organisms.
Subcellular drug distribution: mechanisms and roles in drug efficacy, toxicity, resistance, and targeted delivery
Published in Drug Metabolism Reviews, 2018
Qiao Li, Ting Zhou, Fei Wu, Na Li, Rui Wang, Qing Zhao, Yue-Ming Ma, Ji-Quan Zhang, Bing-Liang Ma
First, the interplay of the subcellular drug distribution between organelles or organelle and the cytosol or cell membrane should be of concern. For example, the uptake of an organic cation compound by the mitochondria could be assumed to be beneficial in lowering the free drug concentration in the cytosol and, hence, maintaining the concentration gradient of the compound across the cell membrane, as well as the negative charge of the inner cell membrane. This process, in turn, facilitated the enhanced uptake of the compound mediated by cell membrane-expressed drug transporters, and the cell membrane potential. Furthermore, removing the organic cation compound from near the inner cell membrane also helped reduce the cell membrane-expressed P-gp-mediated efflux. In addition, drugs may be directly transferred from one organelle to another. Membrane contact sites (MCS) are close appositions between two organelles where both organelle membranes are closely apposed but do not fuze (Elbaz and Schuldiner 2011). ER-based MCS, including ER-mitochondria, ER-lysosomes, ER-Golgi, ER-plasma membrane, have been extensively studied (Elbaz and Schuldiner 2011). MCS facilitate both signaling and a material passage from one cellular compartment to another (Elbaz and Schuldiner 2011). However, whether MCS is involved in drug passage between organelles and, consequently, subcellular drug distribution is unclear.
Interplay between EGFR, E-cadherin, and PTP1B in epidermal homeostasis
Published in Tissue Barriers, 2023
Tessa Arnaud, Fernando Rodrigues-Lima, Mireille Viguier, Frédérique Deshayes
PTP1B is a ubiquitous and abundant intracellular protein Tyrosine Phosphatase (PTP) that interacts with numerous phosphotyrosine proteins present in the cytoplasm, plasma membrane, vesicles, nucleus and intercellular junctions.16,17 Specialized membrane contact sites may be involved in some of these interactions.18 It is the first described PTP among a hundred of the protein tyrosine phosphatase (PTP) family.19,20 The PTP activity of PTP1B relies on the presence of a conserved and nucleophilic catalytic cysteine residue in the P loop of the enzyme.