Phospholipid scramblase 1: an essential component of the nephrocyte slit diaphragm.
Cell Mol Life Sci
; 81(1): 261, 2024 Jun 15.
Article
in En
| MEDLINE
| ID: mdl-38878170
ABSTRACT
Blood ultrafiltration in nephrons critically depends on specialized intercellular junctions between podocytes, named slit diaphragms (SDs). Here, by studying a homologous structure found in Drosophila nephrocytes, we identify the phospholipid scramblase Scramb1 as an essential component of the SD, uncovering a novel link between membrane dynamics and SD formation. In scramb1 mutants, SDs fail to form. Instead, the SD components Sticks and stones/nephrin, Polychaetoid/ZO-1, and the Src-kinase Src64B/Fyn associate in cortical foci lacking the key SD protein Dumbfounded/NEPH1. Scramb1 interaction with Polychaetoid/ZO-1 and Flotillin2, the presence of essential putative palmitoylation sites and its capacity to oligomerize, suggest a function in promoting SD assembly within lipid raft microdomains. Furthermore, Scramb1 interactors as well as its functional sensitivity to temperature, suggest an active involvement in membrane remodeling processes during SD assembly. Remarkably, putative Ca2+-binding sites in Scramb1 are essential for its activity raising the possibility that Ca2+ signaling may control the assembly of SDs by impacting on Scramb1 activity.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Drosophila Proteins
/
Phospholipid Transfer Proteins
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Podocytes
Limits:
Animals
Language:
En
Journal:
Cell Mol Life Sci
/
Cell. mol. life sci
/
Cellular and molecular life sciences
Journal subject:
BIOLOGIA MOLECULAR
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: