Lysosomal solute carrier transporters gain momentum in research

abstract: ...Emerging evidence indicates that lysosome function extends beyond macromolecular degradation. Genetic and functional defects in components of the lysosomal transport machinery cause lysosomal storage disorders implicating the lysosomal solute carrier (SLC) transporters as essential to vital cell processes. The pathophysiology and therapeutic potential of lysosomal SLC transporters are highlighted here, focusing on recent discoveries in autophagic amino acid sensing (SLC38A9), phagocytic regulation in macrophages (SLC29A3, SLC15A3/A4), adenosine triphosphate (ATP) exocytosis in neurotransmission (SLC17A9), and lysosomal transport of maytansine catabolites into the cytoplasm (SLC46A3).

... essential to vital cell processes. The pathophysiology and therapeutic potential of lysosomal SLC transporters are highlighted here, focusing on recent discoveries in autophagic amino acid sensing (SLC38A9), phagocytic regulation in macrophages (SLC29A3, SLC15A3/A4), adenosine triphosphate (ATP) exocytosis in neurotransmission (SLC17A9), and lysosomal transport of maytansine catabolites into the cytoplasm (SLC46A3). National Institutes of Health 1R01CA188464 R03AR063326 Ohio State University Fund source

... substances for melanin synthesis Melanosomes, Plasma membrane Melanocytes, Skin, Eye Regulates melanosome Ph Oculocutaneous Albinism Type IV 26016411 (2015); 26057890 (2015) SLC46A3 FKSG16 Uncharacterized Lysosomes, Plasma membrane Kidney, Liver, Placenta Mediates antibody drug conjugate maytansine efflux from lysosomes 26631267 (2015) SLC48A1 HRG1 Heme 125 M EndoLysosomes Liver, Heart, Muscle, Small Intestine Regulates intracellular heme availability through endolysosomal compartment 16143108

... adenosine triphosphate (ATP) exocytosis, SLC15A3/A4 as a participant in tolllike receptor (TLR) signaling, SLC29A3 as a regulator of nucleoside salvage, and SLC46A3 as a facilitator of antibodydrug conjugate maytansine efflux. mTOR, mammalian target of Rapamycin; RagA, Ragulator A; RagC, Ragulator C. Distinct amino acid transport systems exist in the lysosomal membrane to transit cystine, cysteine, cationic amino acids, dicarboxylic amino acids, and small and large neutral amino acids, as elucidated

... become a widespread concern. Cleavable linker technology, protonsponge effect, ion pair formation, and hydrophobic modification of vectors or cargos are some of the techniques being currently used for effective drug delivery. In some cases, such strategies are harmful, disrupting (endo) lysosomal membranes. In this regard, lysosomal SLCs offer great promise to aid safe efflux of therapeutic cargos from lysosomes. A recent discovery of SLC46A3 facilitating transport of a noncleavable antibodydrug conjugate catabolite to export cargo from the lysosome validates the feasibility of this strategy. 5 Identification and characterization of orphan SLC46A3 identified maytansine as a substrate for SLC46A3, further clarifying the mechanism of noncleavable maytansinebased antibody drug conjugates, including adotrastuzumab emtansine. The discovery of SLC46A3 as a means for antibodydrug conjugates to target cancer cells suggests future investigation will identify other lysosomal SLC transporters with

... al Equilibrative nucleoside transporter 3 deficiency perturbs lysosome function and macrophage homeostasis . Science 335 , 89 92 ( 2012 ). 22174130 4 Ho , T. et al Vesicular expression and release of ATP from dopaminergic neurons of the mouse retina and midbrain . Front. Cell. Neurosci. 9 , 389 ( 2015 ). 26500494 5 Hamblett , K.J. et al SLC46A3 is required to transport catabolites of noncleavable antibody maytansine conjugates from the lysosome to the cytoplasm . Cancer Res. 75

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Gene: SLC46A3 - solute carrier family 46, member 3 - (NCBI)

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