Perilipin membrane integration determines lipid droplet heterogeneity in differentiating adipocytes.
Cell Rep
; 43(4): 114093, 2024 Apr 23.
Article
en En
| MEDLINE
| ID: mdl-38602875
ABSTRACT
The storage of fat within lipid droplets (LDs) of adipocytes is critical for whole-body health. Acute fatty acid (FA) uptake by differentiating adipocytes leads to the formation of at least two LD classes marked by distinct perilipins (PLINs). How this LD heterogeneity arises is an important yet unresolved cell biological problem. Here, we show that an unconventional integral membrane segment (iMS) targets the adipocyte specific LD surface factor PLIN1 to the endoplasmic reticulum (ER) and facilitates high-affinity binding to the first LD class. The other PLINs remain largely excluded from these LDs until FA influx recruits them to a second LD population. Preventing ER targeting turns PLIN1 into a soluble, cytoplasmic LD protein, reduces its LD affinity, and switches its LD class specificity. Conversely, moving the iMS to PLIN2 leads to ER insertion and formation of a separate LD class. Our results shed light on how differences in organelle targeting and disparities in lipid affinity of LD surface factors contribute to formation of LD heterogeneity.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Diferenciación Celular
/
Adipocitos
/
Retículo Endoplásmico
/
Gotas Lipídicas
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Rep
Año:
2024
Tipo del documento:
Article
País de afiliación:
Suiza