Synonyms for sortilin or Related words with sortilin
Examples of "sortilin"
has been shown to interact with GGA1 and GGA2.
participates in interactions within the trans-Golgi network vesicle budding and BDNF signaling pathways.
GGA2 has been shown to interact with RABEP1,
1, BACE2 and CLINT1.
GGA1 has been shown to interact with
1, BACE2, RABEP1 and ARF3.
Given its function in facilitating lysosomal degradation or recycling of ligands in lipid metabolism and the neural system,
likely plays an important role in the underlying mechanisms and pathophysiology of atherogenesis and coronary artery disease, as well as in neurological disorders. For example,
has been identified as an important receptor for brain apolipoprotein E (APOE) metabolism, which is implicated in the underlying mechanisms of Alzheimer’s disease. Interestingly, a significant role for
has recently also been reported in the field of oncology, as it has been detected in several cancer cell lines. Notably, human cancerous epithelial cells exhibited increased levels of
as compared to normal epithelial tissues. Furthermore, it appears that
participates in the progression of breast cancer and contributes to tumor cell adhesion and invasion.
, the p75 co-receptor, has been found in natural killer cells, but with only low levels of neurotrophin receptor. The
co-receptor is believed to work with a neurotrophin homologue that can also cause neurotrophin to alter the immune response.
is a member of the Vps10p sorting receptor family. Crystallization studies of the protein reveal that, when complexed with the ligand neurotensin, the Vps10 ectodomain of
forms a ten-bladed beta-propeller structure with an inner tunnel that contains multiple ligand binding sites. To prevent premature ligand binding during its synthesis, the precursor protein of
contains a 44-amino acid pro-peptide that serves as a chaperone for the Vps10p domain. In addition, two hydrophobic loops have been detected in this domain and act to anchor the protein in the cell membrane.
Recent research into co-receptors for p75, such as the
co-receptor, has implicated sortillin in connection to neurotrophins, a type of nerve growth factor.
(SORT1) is a protein that in humans is encoded by the "SORT1" gene on chromosome 1. This protein is a type I membrane glycoprotein in the vacuolar protein sorting 10 protein (Vps10p) family of sorting receptors. While it is ubiquitously expressed in many tissues,
is most abundant in the central nervous system. At the cellular level,
functions in protein transport between the Golgi apparatus, endosome, lysosome, and plasma membrane, leading to its involvement in multiple biological processes such as glucose and lipid metabolism as well as neural development and cell death. Moreover, the function and role of
is now emerging in several major human diseases such as atherosclerosis and coronary artery disease, Alzheimer’s disease, and cancer. The "SORT1" gene also contains one of 27 loci associated with increased risk of coronary artery disease.
After being processed in the ER, PCSK9 co-localizes with the protein
on its way through the Golgi and trans-Golgi complex. A PCSK9-
interaction is proposed to be required for cellular secretion of PCSK9. In healthy humans, plasma PCSK9 levels directly correlate with plasma
levels, following a diurnal rhythm similar to cholesterol synthesis. Interestingly, the plasma PCSK9 concentration is higher in women compared to men, and the PCSK9 concentrations decrease with age in men but increasein women, suggesting that estrogen level most likely plays a role. PCSK9 gene expression can be regulated by sterol-response element binding proteins (SREBP-1/2), which also controls LDLR expression.
is expressed over a wide range of cell types and tissues such as the brain, spinal cord, adrenal gland, thyroid, B-lymphocytes, adipocytes, skeletal muscle, and heart. As a sorting receptor on the cell surface and on the endoplasmic reticulum-Golgi apparatus within the cell,
is involved in the transport of a wide variety of intracellular proteins between the trans-Golgi network, endosome, lysosome, and secretory granules, as well as the plasma membrane. This molecular function enables
to participate in various biological processes, including the transport of GLUT4 to the plasma membrane of fat and skeletal muscle cells in response to insulin. It also mediates the interaction between proNGF and the p75NTR:sortilin complex by acting as a co-receptor to signal cell death. The fine regulation of the brain-derived neurotrophic factor (BDNF) by
is required for both neuronal and tumor cell survival. Moreover,
has been implicated in LDL-cholesterol metabolism, VLDL secretion, and PCSK9 secretion, and thus plays a role in the development of atherosclerotic lesions. Other processes involving
include endocytosis, negative regulation of lipoprotein lipase activity, myotube differentiation, ossification, and regulation of gene expression.
-related receptor, L(DLR class) A repeats containing is a protein that in humans is encoded by the SORL1 gene.
In 2007, chromosome 1p13.3 was identified as a promising locus through a genome-wide approach in patients with coronary artery disease. Subsequently, accumulating evidence suggests that the "SORT1" gene at the 1p13 locus is an important risk factor for coronary artery disease, which is attributed to lipid metabolism disorders. As the role of
in lipid metabolism and the development of atherosclerosis has been established, a recent study further reported that increased release of soluble
from platelets, measured as circulating
, may be associated with in vivo platelet activation. This observation also indicates that
has a potential application as a clinical biomarker for diagnosis and prognosis. Additionally, a multi-locus genetic risk score study, based on a combination of 27 loci including the "SORT1" gene, identified individuals at increased risk for both incident and recurrent coronary artery disease events, as well as an enhanced clinical benefit from statin therapy. The study was based on a community cohort study (the Malmo Diet and Cancer study) and four additional randomized controlled trials of primary prevention cohorts (JUPITER and ASCOT) and secondary prevention cohorts (CARE and PROVE IT-TIMI 22).
In the development of both the peripheral nervous system (PNS) and the central nervous system (CNS) the p75NTR-neurotrophin binding activates multiple intracellular pathways which are important in regulating apoptosis. Proneurotrophins (proNTs) are neurotrophins which are released as biologically active uncleaved pro-peptides. Unlike mature neurotrophins which bind to the p75NTR with a low affinity, proNTs preferentially bind to the p75NTR with high affinity. The p75NTR contains a death domain on its cytoplasmic tail which when cleaved activates an apoptotic pathway. The binding of a proNT (proNGF or proBDNF) to p75NTR and its
co-receptor (which binds the pro-domain of proNTs) causes a p75NTR-dependent signal transduction cascade. The cleaved death domain of p75NTR activates c-Jun N-terminal kinase (JNK). The activated JNK translocates into the nucleus, where it phosphorylates and transactivates c-Jun. The transactivation of c-Jun results in the transcription of pro-apoptotic factors TFF-a, Fas-L and Bak. The importance of sotilin in p75NTR-mediated apoptosis is exhibited by the fact that the inhibition of
expression in neurons expressing p75NTR suppresses proNGF-mediated apoptosis, and the prevention of proBDNF binding to p75NTR and
abolished apoptotic action. Activation of p75NTR-mediated apoptosis is much more effective in the absence of Trk receptors due to the fact that activated Trk receptors suppress the JNK cascade.
Retromer is a heteropentameric complex which in humans is composed of a less defined membrane-associated sorting nexin dimer (SNX1, SNX2, SNX5, SNX6), and a vacuolar protein sorting (Vps) trimer containing Vps26, Vps29, Vps35. Although the SNX dimer is required for the recruitment of retromer to the endosomal membrane, the cargo binding function of this complex is contributed by the core trimer through the binding of Vps35 subunit to various cargo molecules including M6PR wntless and
. Early study on sorting of acid hydrolases such as carboxypeptidase Y (CPY) in S. cerevisiae mutants has led to the identification of retromer in mediating the retrograde trafficking of the pro-CPY receptor (Vps10) from the endosomes to the TGN.
High affinity binding between proNGF,
, and p75NTR can result in either survival or programmed cell death. Study results indicate that superior cervical ganglia neurons that express both p75NTR and TrkA die when treated with proNGF, while NGF treatment of these same neurons results in survival and axonal growth. Survival and PCD mechanisms are mediated through adaptor protein binding to the death domain of the p75NTR cytoplasmic tail. Survival occurs when recruited cytoplasmic adaptor proteins facilitate signal transduction through tumor necrosis factor receptor members such as TRAF6, which results in the release of nuclear factor κB (NF-κB) transcription activator. NF-κB regulates nuclear gene transcription to promote cell survival. Alternatively, programmed cell death occurs when TRAF6 and neurotrophin receptor interacting factor (NRIF) are both recruited to activate c-Jun N-terminal kinase (JNK); which phosphorylates c-Jun. The activated transcription factor c-Jun regulates nuclear transcription to increase pro-apoptotic gene transcription.
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