CDB25:0003353 CLU — TREM2

Experimentally validated in Human; Orthology-inferred in Mouse, Rat, Frog, Chicken, Macaque, Pig, Dog, Cow, Chimp, Horse, Marmoset, Sheep

Title

Journal:; Year Published:

Abstract

TREM2 Binds to Apolipoproteins, Including APOE and CLU/APOJ, and Thereby Facilitates Uptake of Amyloid-Beta by Microglia.

Neuron, 2016; PubMed, Homo sapiens CLU — Homo sapiens TREM2
ABSTRACT: Genetic variants of TREM2, a protein expressed selectively by microglia in the brain, are associated with Alzheimer's disease (AD). Starting from an unbiased protein microarray screen, we identified a set of lipoprotein particles (including LDL) and apolipoproteins (including CLU/APOJ and APOE) as ligands of TREM2. Binding of these ligands by TREM2 was abolished or reduced by disease-associated mutations. Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL, CLU, and APOE in heterologous cells, whereas TREM2 disease variants were impaired in this activity. Trem2 knockout microglia showed reduced internalization of LDL and CLU. β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up by microglia in a TREM2-dependent fashion. Uptake of Aβ-lipoprotein complexes was reduced in macrophages from human subjects carrying a TREM2 AD variant. These data link three genetic risk factors for AD and reveal a possible mechanism by which mutant TREM2 increases risk of AD. VIDEO ABSTRACT.
Basic Information on CLU
Ligand Name: clusterin
Other Symbols: CLI, APOJ, SGP-2, SP-40, TRPM-2, KUB1, CLU1, CLU2
Ligand Location: secreted based on hpa, perplexity, uniprot
HGNC Gene Symbol Report: CLU
GeneCards: CLU
Functional Annotations for CLU
Gene Ontologies: PAN-GO, AmiGO 2
Expression Profile: Human Protein Atlas (RNA and protein), Human Cell Atlas (RNA), GEPIA cancer vs normal (RNA), GeneCards (RNA and protein)
Disease Annotations: MalaCards, OMIM, Open Targets Platform, DISEASES (text mining), AI summary (LLM)
Interactions with other Receptors for CLU
CLU — LRP2 ・ CLU — LRP8 ・ CLU — PLXNA4 ・ CLU — VLDLR
Basic Information on TREM2
Receptor Name: triggering receptor expressed on myeloid cells 2
Other Symbols: TREM-2, Trem2a, Trem2b, Trem2c
Receptor Location: cell membrane based on perplexity, uniprot
HGNC Gene Symbol Report: TREM2
GeneCards: TREM2
Functional Annotations for TREM2
Gene Ontologies: PAN-GO, AmiGO 2
Expression Profile: Human Protein Atlas (RNA and protein), Human Cell Atlas (RNA), GEPIA cancer vs normal (RNA), GeneCards (RNA and protein)
Disease Annotations: MalaCards, OMIM, Open Targets Platform, DISEASES (text mining), AI summary (LLM)
Interactions with other Ligands for TREM2
APOA1 — TREM2 ・ APOA2 — TREM2 ・ APOB — TREM2 ・ APOE — TREM2 ・ LPA — TREM2
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