Extracellular vesicles (EVs) play a critical role in intercellular communication by transferring microRNAs, lipids, and proteins to neighboring cells. Sortilin, a sorting receptor that directs target proteins to the secretory or endocytic compartments of cells, is found in both EVs and cells. In many human diseases, including cancer and cardiovascular disorders, sortilin expression levels are a...

The complexity and intricacy of nature has recently been illustrated with the role of sortilin in atherosclerosis. Sortilin, a VPS10p sorting receptor initially identified in human brain tissue, suddenly gained much attention from the cardiovascular community as unbiased genome-wide association studies (GWASs) repeatedly demonstrated that single nucleotide polymorphisms (SNPs) at the 1p13.3 loc...

Prion diseases are a group of fatal neurodegenerative disorders caused by prions, which consist mainly of the abnormally folded isoform of prion protein, PrPSc. A pivotal pathogenic event in prion disease is progressive accumulation of prions, or PrPSc, in brains through constitutive conformational conversion of the cellular prion protein, PrPC, into PrPSc. However, the cellular mechanism by wh...

Proneurotrophins mediate neuronal apoptosis using a dual receptor complex of sortilin and p75(NTR). Although p75(NTR) is highly expressed on the plasma membrane and accessible to proneurotrophin ligands, sortilin is primarily localized to intracellular membranes, limiting the formation of a cell surface co-receptor complex. Here, we show that the mammalian p75(NTR) homologue NRH2 critically reg...

background: our preliminary data on the protein expression of sort1 in ovarian carcinoma tissues showed that sortilin was overexpressed in ovarian carcinoma patients and cell lines, while non-malignant ovaries expressed comparably lower amount of this protein. in spite of diverse ligands and also different putative functions of sortilin (ntr3), the function of overexpressed sortilin in ovarian ...

Neurotensin (NTS), a 13-amino acid peptide which is distributed predominantly along gastrointestinal tract, has multiple physiologic and pathologic functions, and its effects are mediated by three distinct NTS receptors (NTSRs). Overexpression and activation of NTS signaling components, especially NTS and/or NTSR1, are closely linked with cancer progression and metastasis in various types of ca...

Progranulin haplo-insufficiency is a main cause of frontotemporal lobar degeneration (FTLD) with TDP-43 aggregates. Previous studies have shown that sortilin regulates progranulin trafficking and is a main determinant of progranulin level in the brain. In this study, we mapped the binding site between progranulin and sortilin. Progranulin binds to the beta-propeller region of sortilin through i...

gene expression profiling of ovarian carcinoma tissues has shown an increase of four-fold expression of sort1 gene. sortilin 1 (ntr-3) is a 95-100 kda protein normally expressed in heart, brain, placenta, skeletal muscle, spinal cord, thyroid, and testis. however, its expression has never been reported in normal ovary. here, we report expression of sortilin 1 in ovarian carcinoma tissues both a...

Regulating the transcription, translation and secretion of cytokines is crucial for controlling the appropriate balance of inflammation. Here we report that the sorting receptor sortilin plays a key role in cytokine production. We observed interactions of sortilin with multiple cytokines including IFN-α, and sortilin depletion in plasmacytoid dendritic cells (pDCs) led to a reduction of IFN-α s...

The neurotensin receptor-3 also known as sortilin was the first member of the small family of vacuolar protein sorting 10 protein domain (Vps10p) discovered two decades ago in the human brain. The expression of sortilin is not confined to the nervous system but sortilin is ubiquitously expressed in many tissues. Sortilin has multiple roles in the cell as a receptor or a co-receptor, in protein ...