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Retromer
Retromer is a complex of proteins that has been shown to be important in recycling transmembrane receptors from endosomes to the Golgi apparatus, ''trans''-Golgi network (TGN). Background 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 VPS26A, Vps26, VPS29, Vps29, VPS35, 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 cation-dependent mannose-6-phosphate receptor, M6PR GPR177, wntless and sortilin 1, sortilin. 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 (SORCS1, Vp ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
VPS35
Vacuolar protein sorting ortholog 35 (VPS35) is a protein involved in autophagy and is implicated in Neurodegeneration, neurodegenerative diseases, such as Parkinson's disease (PD) and Alzheimer's disease (AD). VPS35 is part of a complex called the retromer, which is responsible for transporting select cargo proteins between vesicular structures (e.g., endosomes, lysosomes, vacuoles) and the Golgi apparatus. Mutations in the VPS35 gene (''VPS35'') cause aberrant autophagy, where cargo proteins fail to be transported and dysfunctional or unnecessary proteins fail to be degraded. There are numerous pathways affected by altered ''VPS35'' levels and activity, which have clinical significance in neurodegeneration. There is therapeutic relevance for VPS35, as interventions aimed at correcting VPS35 function are in speculation. Gene In humans, ''VPS35'' is Transcription (biology), transcribed on chromosome 16q11.2 where is spans about 29.6 kilobases and contains 17 exons. It is Conserve ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Retromer Protein Complex
Retromer is a complex of proteins that has been shown to be important in recycling transmembrane receptors from endosomes to the ''trans''-Golgi network (TGN). Background 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 sortilin. 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. Structure The retromer complex is highly conserved: homologs ha ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
VPS26A
Vacuolar protein sorting-associated protein 26A is a protein that in humans is encoded by the ''VPS26A'' gene. This gene belongs to a group of vacuolar protein sorting (VPS) genes. The encoded protein is a component of a large multimeric complex, termed the retromer complex, involved in retrograde transport of proteins from endosomes to the trans-Golgi network. The close structural similarity between the yeast and human proteins that make up this complex suggests a similarity in function. Expression studies in yeast and mammalian cells indicate that this protein interacts directly with VPS35, which serves as the core of the retromer complex. Alternative splicing results in multiple transcript variants encoding different isoforms. Structure Vps26 is a 38-kDa subunit that has a two-lobed structure with a polar core that resembles the arrestin family of trafficking adaptor. This fold consist of two related β-sandwich subdomains with a fibronectin type III domain topology. The tw ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
VPS29
VPS29 is a human gene coding for the vacuolar protein sorting protein Vps29, a component of the retromer complex. Yeast homolog The homologous protein (one that performs the same function) in yeast is Vacuolar protein sorting 29 homolog (S. cerevisiae). Function VPS29 belongs to a group of genes coding for vacuolar protein sorting (VPS) proteins that, when functionally impaired, disrupt the efficient delivery of vacuolar hydrolases. The protein encoded by this gene, Vps29, is a component of a large multimeric complex, termed the retromer complex, which is involved in retrograde transport of proteins from endosomes to the trans-Golgi network. Vps29 may be involved in the formation of the inner shell of the retromer coat for retrograde vesicles leaving the prevacuolar compartment. Alternative splice variants encoding different isoforms, and usage of multiple polyadenylation Polyadenylation is the addition of a poly(A) tail to an RNA transcript, typically a messenger RNA (mRNA). ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
SNX1
Sorting nexin-1 is a protein that in humans is encoded by the SNX1 gene. The protein encoded by this gene is a sorting nexin. SNX1 is a component of the retromer complex. Function This gene encodes a member of the sorting nexin family. Members of this family contain a phox ( PX) domain, which is a phosphoinositide binding domain, and are involved in intracellular trafficking. This endosomal protein regulates the cell-surface expression of epidermal growth factor receptor. This protein also has a role in sorting protease-activated receptor-1 from early endosomes to lysosome A lysosome () is a membrane-bound organelle found in many animal cells. They are spherical vesicles that contain hydrolytic enzymes that can break down many kinds of biomolecules. A lysosome has a specific composition, of both its membrane prot ...s. This protein may form oligomeric complexes with other family members. References Further reading * * * * * * * * * * * * * * * * * * * External li ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
SNX6
Sorting Nexin 6 also known as SNX6 is a well-conserved membrane-associated protein belonging to the sorting nexin family that is a component of the retromer complex. The protein contains a coiled-coil domain at its C terminus and a PX domain at its N terminus. Binding to PIM1 causes translocation to the nucleus. SNX6 has been shown to associate with TRAF4 TNF receptor-associated factor 4 (TRAF4) also known as RING finger protein 83 (RNF83) is a protein that in humans is encoded by the ''TRAF4'' gene. TRAF4 is a member of the TNF receptor associated factor (TRAF) family, a family of scaffold protein .... References {{gene-14-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Endosomal
Endosomes are a collection of intracellular sorting organelles in eukaryotic cells. They are parts of endocytic membrane transport pathway originating from the trans Golgi network. Molecules or ligands internalized from the plasma membrane can follow this pathway all the way to lysosomes for degradation or can be recycled back to the cell membrane in the endocytic cycle. Molecules are also transported to endosomes from the trans Golgi network and either continue to lysosomes or recycle back to the Golgi apparatus. Endosomes can be classified as early, sorting, or late depending on their stage post internalization. Endosomes represent a major sorting compartment of the endomembrane system in cells. Function Endosomes provide an environment for material to be sorted before it reaches the degradative lysosome. For example, low-density lipoprotein (LDL) is taken into the cell by binding to the LDL receptor at the cell surface. Upon reaching early endosomes, the LDL dissociates ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Endosome
Endosomes are a collection of intracellular sorting organelles in eukaryotic cells. They are parts of endocytic membrane transport pathway originating from the trans Golgi network. Molecules or ligands internalized from the plasma membrane can follow this pathway all the way to lysosomes for degradation or can be recycled back to the cell membrane in the endocytic cycle. Molecules are also transported to endosomes from the trans Golgi network and either continue to lysosomes or recycle back to the Golgi apparatus. Endosomes can be classified as early, sorting, or late depending on their stage post internalization. Endosomes represent a major sorting compartment of the endomembrane system in cells. Function Endosomes provide an environment for material to be sorted before it reaches the degradative lysosome. For example, low-density lipoprotein (LDL) is taken into the cell by binding to the LDL receptor at the cell surface. Upon reaching early endosomes, the LDL dissociates ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
SNX2
Sorting nexin-2 is a protein that in humans is encoded by the ''SNX2'' gene. Function This gene encodes a member of the sorting nexin family. Members of this family contain a phox (PX) domain, which is a phosphoinositide binding domain, and are involved in intracellular trafficking. This protein associates with formin-binding protein 17, but its function is unknown. This protein may form oligomeric complexes with family members. Interactions SNX2 has been shown to interact with FNBP1 Formin-binding protein 1 is a protein that in humans is encoded by the ''FNBP1'' gene. Function The protein encoded by this gene is a member of the formin-binding-protein family. The protein contains an N-terminal Fer/Cdc42-interacting protein .... References Further reading * * * * * * * * * * * * * * * {{Gene-5-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
SNX5
Sorting nexin-5 is a protein that in humans is encoded by the ''SNX5'' gene. This gene encodes a member of the sorting nexin family. Members of this family contain a phox (PX) domain, which is a phosphoinositide binding domain, and are involved in intracellular trafficking. This protein is a component of the mammalian retromer complex, which facilitates cargo retrieval from endosomes to the trans-Golgi network. It has also been shown to bind to the Fanconi anemia, complementation group A protein. This gene results in two transcript variants encoding the same protein. Model organisms Model organisms have been used in the study of SNX5 function. A conditional knockout mouse line, called ''Snx5tm1a(KOMP)Wtsi'' was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute. Male and female animals underwent a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Wnt Signaling Pathway
The Wnt signaling pathways are a group of signal transduction pathways which begin with proteins that pass signals into a cell through cell surface receptors. The name Wnt is a portmanteau created from the names Wingless and Int-1. Wnt signaling pathways use either nearby cell-cell communication (paracrine) or same-cell communication (autocrine). They are highly evolutionarily conserved in animals, which means they are similar across animal species from fruit flies to humans. Three Wnt signaling pathways have been characterized: the canonical Wnt pathway, the noncanonical planar cell polarity pathway, and the noncanonical Wnt/calcium pathway. All three pathways are activated by the binding of a Wnt-protein ligand to a Frizzled family receptor, which passes the biological signal to the Dishevelled protein inside the cell. The canonical Wnt pathway leads to regulation of gene transcription, and is thought to be negatively regulated in part by the SPATS1 gene. The noncanonical plana ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
GPR177
Protein wntless homolog, commonly known as Wntless, is encoded in humans by the ''WLS'' gene . Wntless is a receptor for Wnt proteins in Wnt-secreting cells. Wntless was shown to be a cargo for the retromer complex. It has been found essential for hair follicle induction. A homozygous missense mutation In genetics, a missense mutation is a point mutation in which a single nucleotide change results in a codon that codes for a different amino acid. It is a type of nonsynonymous substitution. Substitution of protein from DNA mutations Missense m ... in the ''WLS'' gene was identified in Zaki syndrome. References Further reading * * * * See also * {{G protein-coupled receptors G protein-coupled receptors ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
