Endolysosomal Cation Channels of the Transient Receptor Potential Superfamily

Christian Grimm

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Lysosomes are cell organelles involved in the breakdown of proteins, lipids, and other molecules and have been implicated not only...

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Lysosomes are cell organelles involved in the breakdown of proteins, lipids, and other molecules and have been implicated not only in endolysosomal storage disorders (LSDs) such as mucolipidoses or mucopolysaccharidoses but also in metabolic diseases, neurodegenerative disorders such as Alzheimer's and Parkinson's disease, pigmentation disorders, or infectious diseases. Highly critical for the proper function of lysosomes, endosomes, and lysosome-related organelles is the tight regulation of various fusion and fission processes and the regulation of proton and other ionic concentrations within the endolysosomal system. Calcium permeable, non-selective cation channels of the TRP (transient receptor potential) superfamily, namely TRPML channels (mucolipins) and TPCs (two-pore channels) have been found to play important roles in these processes. This thesis provides insights into the function and physiology of TRPML and TPC channels, explains the molecular basis of pathologies associated with diseases caused by loss or mutation of these channels, and discusses potential therapeutic approaches.
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Professorial Dissertation from the year 2014 in the subject Medicine - Pharmacology, grade: Passed, LMU Munich (Pharmacy/Pharmacology), language: English, abstract: Lysosomes are cell organelles involved in the breakdown of proteins, lipids, and other molecules and have been implicated not only in endolysosomal storage disorders (LSDs) such as mucolipidoses or mucopolysaccharidoses but also in metabolic diseases, neurodegenerative disorders such as Alzheimer's and Parkinson's disease, pigmentation disorders, or infectious diseases. Highly critical for the proper function of lysosomes, endosomes, and lysosome-related organelles is the tight regulation of various fusion and fission processes and the regulation of proton and other ionic concentrations within the endolysosomal system. Calcium permeable, non-selective cation channels of the TRP (transient receptor potential) superfamily, namely TRPML channels (mucolipins) and TPCs (two-pore channels) have been found to play important roles in these processes. This thesis provides insights into the function and physiology of TRPML and TPC channels, explains the molecular basis of pathologies associated with diseases caused by loss or mutation of these channels, and discusses potential therapeutic approaches.