Modulation of PICALM Levels Perturbs Cellular Cholesterol Homeostasis.
Modulation of PICALM Levels Perturbs Cellular Cholesterol Homeostasis.
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DOI：
10.1371/journal.pone.0129776
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Wechsler DS
中科院分区：
文献类型：
--
作者：
Mercer JL;Argus JP;Crabtree DM;Keenan MM;Wilks MQ;Chi JT;Bensinger SJ;Lavau CP;Wechsler DS
PICALM (Phosphatidyl Inositol Clathrin Assembly Lymphoid Myeloid protein) is a ubiquitously expressed protein that plays a role in clathrin-mediated endocytosis. PICALM also affects the internalization and trafficking of SNAREs and modulates macroautophagy. Chromosomal translocations that result in the fusion of PICALM to heterologous proteins cause leukemias, and genome-wide association studies have linked PICALM Single Nucleotide Polymorphisms (SNPs) to Alzheimer’s disease. To obtain insight into the biological role of PICALM, we performed gene expression studies of PICALM-deficient and PICALM-expressing cells. Pathway analysis demonstrated that PICALM expression influences the expression of genes that encode proteins involved in cholesterol biosynthesis and lipoprotein uptake. Gas Chromatography-Mass Spectrometry (GC-MS) studies indicated that loss of PICALM increases cellular cholesterol pool size. Isotopic labeling studies revealed that loss of PICALM alters increased net scavenging of cholesterol. Flow cytometry analyses confirmed that internalization of the LDL receptor is enhanced in PICALM-deficient cells as a result of higher levels of LDLR expression. These findings suggest that PICALM is required for cellular cholesterol homeostasis and point to a novel mechanism by which PICALM alterations may contribute to disease.
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影响因子：
4.8
作者：
Garuti, R;Jones, C;Hobbs, HH
通讯作者：
Hobbs, HH
DOI：
10.1083/jcb.200207113
发表时间：
2003-01-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ehehalt R;Keller P;Haass C;Thiele C;Simons K
通讯作者：
Simons K
影响因子：
11.4
作者：
Bohlander, SK;Muschinsky, V;Dreyling, MH
通讯作者：
Dreyling, MH
DOI：
10.1186/bcr2899
发表时间：
2011-06-07
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Gatza ML;Kung HN;Blackwell KL;Dewhirst MW;Marks JR;Chi JT
通讯作者：
Chi JT
DOI：
10.1073/pnas.93.10.4804
发表时间：
1996-05-14
影响因子：
11.1
作者：
Dreyling, MH;MartinezCliment, JA;Bohlander, SK
通讯作者：
Bohlander, SK