Loss of mfsd8 alters the secretome during Dictyostelium aggregation DOI Creative Commons
Robert J. Huber, Joshua P. Gray, William D. Kim

и другие.

European Journal of Cell Biology, Год журнала: 2023, Номер 102(4), С. 151361 - 151361

Опубликована: Сен. 19, 2023

Major facilitator superfamily domain-containing protein 8 (MFSD8) is a transmembrane that has been reported to function as lysosomal chloride channel. In humans, homozygous mutations in MFSD8 cause late-infantile form of neuronal ceroid lipofuscinosis (NCL) called CLN7 disease. the social amoeba Dictyostelium discoideum, Mfsd8 localizes cytoplasmic puncta and vesicles, regulates conserved processes during organism's life cycle. Here, we used D. discoideum examine effect mfsd8-deficiency on secretome early stages multicellular development. Mass spectrometry revealed 61 proteins were differentially released by cells after 4 hours starvation. Most present increased amounts mfsd8- conditioned buffer compared WT indicating loss mfsd8 deregulates secretion and/or causes release not normally secreted cells. GO term enrichment analyses showed many aberrantly localize compartments regions cell associated with endo-lysosomal secretory pathways. also previously known be impacted (e.g., cathepsin D), well may underlie phenotypes aggregation. Finally, show reduces intracellular proteasome 20 S activity due abnormal at least one proteasomal subunit. Together, this study reveals impact aggregation lays foundation for follow up work investigates role altered

Язык: Английский

Pathological Functions of Lysosomal Ion Channels in the Central Nervous System DOI Open Access

Jian-Ke Cen,

Nan Hu,

Jiawen Shen

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(12), С. 6565 - 6565

Опубликована: Июнь 14, 2024

Lysosomes are highly dynamic organelles that maintain cellular homeostasis and regulate fundamental processes by integrating multiple metabolic pathways. Lysosomal ion channels such as TRPML1-3, TPC1/2, ClC6/7, CLN7, TMEM175 mediate the flux of Ca2+, Cl−, Na+, H+, K+ across lysosomal membranes in response to osmotic stimulus, nutrient-dependent signals, stresses. These serve crucial transducers cell signals essential for regulation biogenesis, motility, membrane contact site formation, homeostasis. In terms pathophysiology, genetic variations these channel genes have been associated with development storage diseases, neurodegenerative inflammation, cancer. This review aims discuss current understanding role central nervous system assess their potential drug targets.

Язык: Английский

Процитировано

1
Loss of mfsd8 alters the secretome during Dictyostelium aggregation DOI Creative Commons
Robert J. Huber, Joshua P. Gray, William D. Kim

и другие.

European Journal of Cell Biology, Год журнала: 2023, Номер 102(4), С. 151361 - 151361

Опубликована: Сен. 19, 2023

Major facilitator superfamily domain-containing protein 8 (MFSD8) is a transmembrane that has been reported to function as lysosomal chloride channel. In humans, homozygous mutations in MFSD8 cause late-infantile form of neuronal ceroid lipofuscinosis (NCL) called CLN7 disease. the social amoeba Dictyostelium discoideum, Mfsd8 localizes cytoplasmic puncta and vesicles, regulates conserved processes during organism's life cycle. Here, we used D. discoideum examine effect mfsd8-deficiency on secretome early stages multicellular development. Mass spectrometry revealed 61 proteins were differentially released by cells after 4 hours starvation. Most present increased amounts mfsd8- conditioned buffer compared WT indicating loss mfsd8 deregulates secretion and/or causes release not normally secreted cells. GO term enrichment analyses showed many aberrantly localize compartments regions cell associated with endo-lysosomal secretory pathways. also previously known be impacted (e.g., cathepsin D), well may underlie phenotypes aggregation. Finally, show reduces intracellular proteasome 20 S activity due abnormal at least one proteasomal subunit. Together, this study reveals impact aggregation lays foundation for follow up work investigates role altered

Язык: Английский

Процитировано

2