TY - JOUR
T1 - The phospholipid flippase ATP8B1 is required for lysosomal fusion in macrophages
AU - Gómez-Mellado, Valentina E.
AU - Ho-Mok, Kam S.
AU - van der Mark, Vincent A.
AU - van der Wel, Nicole N.
AU - Grootemaat, Anita E.
AU - Verhoeven, Arthur J.
AU - Elferink, Ronald P. J. Oude
AU - Paulusma, Coen C.
N1 - Funding Information: We thank Drs. Simon Syvertsson and Leendert Hamoen for providing us with the ‐GFP strain. We are also grateful to Dr. P. J. Bosma for critical reading of the manuscript. V. G. M. was supported by a Tytgat Institute Grant. E. coli Publisher Copyright: © 2022 The Authors. Cell Biochemistry and Function published by John Wiley & Sons Ltd.
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
KW - ATP8B1
KW - CDC50A
KW - PFIC1
KW - flippase
KW - late endosomes
KW - lysosomal fusion
KW - multivesicular bodies
KW - phospholipid
UR - http://www.scopus.com/inward/record.url?scp=85138745240&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/cbf.3752
DO - https://doi.org/10.1002/cbf.3752
M3 - Article
C2 - 36169099
SN - 0263-6484
VL - 40
SP - 914
EP - 925
JO - Cell biochemistry and function
JF - Cell biochemistry and function
IS - 8
ER -