| First Author | Hölttä-Vuori M | Year | 2012 |
| Journal | Circ Res | Volume | 110 |
| Issue | 3 | Pages | 450-5 |
| PubMed ID | 22223354 | Mgi Jnum | J:192698 |
| Mgi Id | MGI:5466222 | Doi | 10.1161/CIRCRESAHA.111.256842 |
| Citation | Holtta-Vuori M, et al. (2012) Endosomal actin remodeling by coronin-1A controls lipoprotein uptake and degradation in macrophages. Circ Res 110(3):450-5 |
| abstractText | RATIONALE: The actin cytoskeleton has been implicated in the processing of atherogenic lipoproteins in macrophages. However, the functional role of actin and the regulatory proteins involved are unknown. OBJECTIVE: Coronin-1A (Coro1A) was identified as a differentially expressed transcript in wild-type versus Niemann-Pick type C1 deficient macrophages exposed to acetylated low-density lipoproteins (AcLDL). We investigated whether Coro1A plays a role in the uptake or processing of modified lipoproteins in macrophages and if this is related to its actin regulatory functions. METHODS AND RESULTS: In wild-type primary macrophages, filamentous actin transiently decorated AcLDL containing endosomes that also recruited Coro1A. This dynamic association of F-actin with endosomes was disturbed in Coro1A deficient macrophages. In Coro1A knockout macrophages the uptake of AcLDL was increased, rate of AcLDL delivery to lysosomes enhanced, and lipoprotein-derived cholesteryl ester hydrolysis accelerated. Overexpression of wild-type Coro1A normalized AcLDL uptake in Coro1A knockout macrophages while a Coro1A actin binding mutant did not. Furthermore, the effects of macrophage Coro1A silencing on endosomal actin association and AcLDL delivery to lysosomes resembled those of cofilin silencing. CONCLUSIONS: Coro1A controls actin association with endocytic organelles, thereby negatively regulating endo-lysosomal delivery, degradation of modified lipoproteins and cholesterol deposition in macrophages. |
