RRC ID 80974
Author Castillo-Mancho V, Atienza-Manuel A, Sarmiento-Jiménez J, Ruiz-Gómez M, Culi J.
Title Phospholipid scramblase 1: an essential component of the nephrocyte slit diaphragm.
Journal Cell Mol Life Sci
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.
Volume 81(1)
Pages 261
Published 2024-6-15
DOI 10.1007/s00018-024-05287-z
PII 10.1007/s00018-024-05287-z
PMID 38878170
MeSH Animals Drosophila Proteins* / genetics Drosophila Proteins* / metabolism Drosophila melanogaster / genetics Drosophila melanogaster / metabolism Intercellular Junctions / metabolism Membrane Microdomains / metabolism Membrane Proteins / genetics Membrane Proteins / metabolism Phospholipid Transfer Proteins* / genetics Phospholipid Transfer Proteins* / metabolism Podocytes* / metabolism
Drosophila 18495R-3 11981R-3 4904R-2