| Autor: |
Gómez‐Mellado, Valentina E., Ho‐Mok, Kam S., van der Mark, Vincent A., van der Wel, Nicole N., Grootemaat, Anita E., Verhoeven, Arthur J., Elferink, Ronald P. J. Oude, Paulusma, Coen C. |
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| Zdroj: |
Cell Biochemistry & Function; Dec2022, Vol. 40 Issue 8, p914-925, 12p |
| Abstrakt: |
ATP8B1 is a phospholipid flippase and member of the type 4 subfamily of P‐type ATPases (P4‐ATPase) subfamily. P4‐ATPases catalyze the translocation of phospholipids across biological membranes, ensuring proper membrane asymmetry, which is crucial for membrane protein targeting and activity, vesicle biogenesis, and barrier function. Here we have investigated the role of ATP8B1 in the endolysosomal pathway in macrophages. Depletion of ATP8B1 led to delayed degradation of content in the phagocytic pathway and in overacidification of the endolysosomal system. Furthermore, ATP8B1 knockdown cells exhibited large multivesicular bodies filled with intraluminal vesicles. Similar phenotypes were observed in CRISPR‐generated ATP8B1 knockout cells. Importantly, induction of autophagy led to accumulation of autophagosomes in ATP8B1 knockdown cells. Collectively, our results support a novel role for ATP8B1 in lysosomal fusion in macrophages, a process crucial in the terminal phase of endolysosomal degradation. Significance statement: ATP8B1 belongs to the P4‐ATPase family of lipid flippases of which the cellular and physiological functions remain elusive. ATP8B1 deficiency causes a severe hereditary liver disorder in humans, but also many extrahepatic problems, of which the etiology remains unclear. Our work presents novel insights into the cellular functions of ATP8B1 and may be of interest to basic and translational researchers as well as to physicians. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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