| Endosomal Actin Remodeling by Coronin-1A Controls Lipoprotein Uptake and Degradation in Macrophages. | |
| | |
MedLine Citation:
|
PMID: 22223354 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
Maarit Hölttä-Vuori; Saara Vainio; Maria Kauppi; Miranda Van Eck; Eija Jokitalo; Elina Ikonen |
Related Documents
:
|
1591234 - Increased susceptibility to activation and increased uptake of low density lipoprotein ... 12667094 - Macrophage migration inhibitory factor. 11477084 - The uptake and degradation of matrix-bound lipoproteins by macrophages require an intac... 10648004 - Surface expression and rapid internalization of macrosialin (mouse cd68) on elicited mo... 8642244 - A bcl-2 transgene expressed in hepatocytes protects mice from fulminant liver destructi... 10322394 - Regulation of apoptosis in the prostate gland by androgenic steroids. |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2012-1-5 |
Journal Detail:
|
Title: Circulation research Volume: - ISSN: 1524-4571 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
|
Created Date: 2012-1-6 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0047103 Medline TA: Circ Res Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
Institute of Biomedicine/Anatomy, University of Helsinki, Finland; Division of Biopharmaceuticals, Leiden/Amsterdam Center for Drug Research, Leiden University, the Netherlands; Institute of Biotechnology, University of Helsinki, Finland. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Shortened Ca2+ signaling refractoriness underlies cellular arrhythmogenesis in a postinfarction mode...
Next Document: Left-right symmetry breaking in tissue morphogenesis via cytoskeletal mechanics.