Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0024312 (
lymphopenia
)
4,859
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
ATP11A and
ATP11C
, members of the P4-ATPases, are flippases that translocate phosphatidylserine (PtdSer) from the outer to inner leaflet of the plasma membrane. Using the W3 T lymphoma cell line, we found that Ca
2+
ionophore-induced phospholipid scrambling caused prolonged PtdSer exposure in cells lacking both the
ATP11A
and
ATP11C
genes.
ATP11C
-null (
ATP11C
-/y
) mutant mice exhibit severe B-cell deficiency. In wild-type mice,
ATP11C
was expressed at all B-cell developmental stages, while ATP11A was not expressed after pro-B-cell stages, indicating that
ATP11C
-/y
early B-cell progenitors lacked plasma membrane flippases. The receptor kinases MerTK and Axl are known to be essential for the PtdSer-mediated engulfment of apoptotic cells by macrophages.
MerTK
-/-
and
Axl
-/-
double deficiency fully rescued the
lymphopenia
in the
ATP11C
-/y
bone marrow. Many of the rescued
ATP11C
-/y
pre-B and immature B cells exposed PtdSer, and these cells were engulfed alive by wild-type peritoneal macrophages, in a PtdSer-dependent manner. These results indicate that ATP11A and
ATP11C
in precursor B cells are essential for rapidly internalizing PtdSer from the cell surface to prevent the cells' engulfment by macrophages.
...
PMID:Phospholipid flippases enable precursor B cells to flee engulfment by macrophages. 3044 13
