The Experts below are selected from a list of 30117 Experts worldwide ranked by ideXlab platform
Hans-peter Hauri - One of the best experts on this subject based on the ideXlab platform.
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mapk signaling to the early Secretory Pathway revealed by kinase phosphatase functional screening
Journal of Cell Biology, 2010Co-Authors: Hesso Farhan, Markus W Wendeler, Sandra Mitrovic, Eugenio Fava, Yael Silberberg, Roded Sharan, Marino Zerial, Hans-peter HauriAbstract:To what extent the Secretory Pathway is regulated by cellular signaling is unknown. In this study, we used RNA interference to explore the function of human kinases and phosphatases in controlling the organization of and trafficking within the Secretory Pathway. We identified 122 kinases/phosphatases that affect endoplasmic reticulum (ER) export, ER exit sites (ERESs), and/or the Golgi apparatus. Numerous kinases/phosphatases regulate the number of ERESs and ER to Golgi protein trafficking. Among the Pathways identified, the Raf–MEK (MAPK/ERK [extracellular signal-regulated kinase] kinase)–ERK cascade, including its regulatory proteins CNK1 (connector enhancer of the kinase suppressor of Ras-1) and neurofibromin, controls the number of ERESs via ERK2, which targets Sec16, a key regulator of ERESs and COPII (coat protein II) vesicle biogenesis. Our analysis reveals an unanticipated complexity of kinase/phosphatase-mediated regulation of the Secretory Pathway, uncovering a link between growth factor signaling and ER export.
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Capturing protein interactions in the Secretory Pathway of living cells.
Proceedings of the National Academy of Sciences of the United States of America, 2005Co-Authors: Beat Nyfeler, Stephen W. Michnick, Hans-peter HauriAbstract:The Secretory Pathway is composed of membrane compartments specialized in protein folding, modification, transport, and sorting. Numerous transient protein-protein interactions guide the transport-competent proteins through the Secretory Pathway. Here we have adapted the yellow fluorescent protein (YFP)-based protein fragment complementation assay (PCA) to detect protein-protein interactions in the Secretory Pathway of living cells. Fragments of YFP were fused to the homooligomeric cargo-receptor lectin endoplasmic reticulum Golgi intermediate compartment (ERGIC)-53, to the ERGIC-53-interacting multicoagulation factor deficiency protein MCFD2, and to ERGIC-53's cargo glycoprotein cathepsin Z. YFP PCA analysis revealed the oligomerization of ERGIC-53 and its interaction with MCFD2, as well as its lectin-mediated interaction with cathepsin Z. Mutation of the lectin domain of ERGIC-53 selectively decreased YFP complementation with cathepsin Z. Using YFP PCA, we discovered a carbohydrate-mediated interaction between ERGIC-53 and cathepsin C. We conclude that YFP PCA can detect weak and transient protein interactions in the Secretory Pathway and hence is a powerful approach to study luminal processes involved in protein secretion. The study extends the application of PCA to carbohydrate-mediated protein-protein interactions of low affinity.
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Lectins and protein traffic early in the Secretory Pathway.
Biochemical Society Symposia, 2002Co-Authors: Hans-peter Hauri, O Nufer, Lionel Breuza, Houchaima Ben Tekaya, Lu LiangAbstract:Lectins of the early Secretory Pathway are involved in selective transport of newly synthesized glycoproteins from the endoplasmic reticulum (ER) to the ER-Golgi intermediate compartment (ERGIC). The most prominent cycling lectin is the mannose-binding type I membrane protein ERGIC-53 (ERGIC protein of 53 kDa), a marker for the ERGIC, which functions as a cargo receptor to facilitate export of an increasing number of glycoproteins with different characteristics from the ER. Two ERGIC-53-related proteins, VIP36 (vesicular integral membrane protein 36) and a novel ERGIC-53-like protein, ERGL, are also found in the early Secretory Pathway. ERGL may act as a regulator of ERGIC-53. Studies of ERGIC-53 continue to provide new insights into the organization and dynamics of the early Secretory Pathway. Analysis of the cycling of ERGIC-53 uncovered a complex interplay of trafficking signals and revealed novel cytoplasmic ER-export motifs that interact with COP-II coat proteins. These motifs are common to type I and polytopic membrane proteins including presenilin 1 and presenilin 2. The results support the notion that protein export from the ER is selective.
Francis S Lee - One of the best experts on this subject based on the ideXlab platform.
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sortilin controls intracellular sorting of brain derived neurotrophic factor to the regulated Secretory Pathway
The Journal of Neuroscience, 2005Co-Authors: Zheyu Chen, Alessandro Ieraci, Henry Teng, Henning Dall, Chuixiang Meng, Daniel G Herrera, Anders Nykjaer, Barbara L Hempstead, Francis S LeeAbstract:Brain-derived neurotrophic factor (BDNF), after activity-dependent secretion from neurons, modulates critical nervous system functions. Recently, a variant in the human bdnf gene, resulting in a valine to methionine substitution in the prodomain, has been shown to lead to defective regulated secretion from neurons and memory impairment. Here, we report a novel function for a Vps10p domain protein, sortilin, in controlling BDNF sorting to the regulated Secretory Pathway. Sortilin interacts specifically with BDNF in a region encompassing the methionine substitution and colocalizes with BDNF in Secretory granules in neurons. A truncated form of sortilin causes BDNF missorting to the constitutive Secretory Pathway without affecting neurotrophin-4 (NT-4) secretion. In addition, sortilin small interfering RNA introduced into primary neurons also led to BDNF missorting from the regulated to the constitutive Secretory Pathway. Together, these data suggest a mechanism to understand the defect associated with variant BDNF and provide a framework, based on divergent presynaptic regulation of sorting to Secretory Pathways, to explain how two ligands for tropomyosin-related kinase B, BDNF and NT-4, can mediate diverse biological responses.
Gerard J. M. Martens - One of the best experts on this subject based on the ideXlab platform.
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Prohormone transport through the Secretory Pathway of neuroendocrine cells.
Biochemistry and Cell Biology, 2000Co-Authors: Roland P. Kuiper, Gerard J. M. MartensAbstract:En route through the Secretory Pathway of neuroendocrine cells, prohormones pass a series of membrane-bounded compartments. During this transport, the prohormones are sorted to Secretory granules a...
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7B2 is a neuroendocrine chaperone that transiently interacts with prohormone convertase PC2 in the Secretory Pathway.
Cell, 1994Co-Authors: Joanna A. M. Braks, Gerard J. M. MartensAbstract:Abstract The neuroendocrine polypeptide 7B2 is a highly conserved Secretory protein selectively present in prohormone-producing cells equipped with a regulated Secretory Pathway. We find that the amino-terminal half of 7B2 is distantly related to chaperonins, a subclass of molecular chaperones. When incubated in vitro with newly synthesized pituitary proteins, recombinant 7B2 specifically associates with prohormone convertase PC2. Metabolic cell labeling combined with coimmuno-precipitation studies showed that, in vivo, the precursor form of 7B2 interacts with the proform of PC2. Pulse-chase analysis revealed that this association is transient in that it commences early in the Secretory Pathway, while dissociation in the later stages appears to coincide with the cleavages of 7B2, proPC2, and prohormone. Our results suggest that 7B2 is a novel type of molecular chaperone preventing premature activation of proPC2 in the regulated Secretory Pathway.
Zheyu Chen - One of the best experts on this subject based on the ideXlab platform.
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sortilin controls intracellular sorting of brain derived neurotrophic factor to the regulated Secretory Pathway
The Journal of Neuroscience, 2005Co-Authors: Zheyu Chen, Alessandro Ieraci, Henry Teng, Henning Dall, Chuixiang Meng, Daniel G Herrera, Anders Nykjaer, Barbara L Hempstead, Francis S LeeAbstract:Brain-derived neurotrophic factor (BDNF), after activity-dependent secretion from neurons, modulates critical nervous system functions. Recently, a variant in the human bdnf gene, resulting in a valine to methionine substitution in the prodomain, has been shown to lead to defective regulated secretion from neurons and memory impairment. Here, we report a novel function for a Vps10p domain protein, sortilin, in controlling BDNF sorting to the regulated Secretory Pathway. Sortilin interacts specifically with BDNF in a region encompassing the methionine substitution and colocalizes with BDNF in Secretory granules in neurons. A truncated form of sortilin causes BDNF missorting to the constitutive Secretory Pathway without affecting neurotrophin-4 (NT-4) secretion. In addition, sortilin small interfering RNA introduced into primary neurons also led to BDNF missorting from the regulated to the constitutive Secretory Pathway. Together, these data suggest a mechanism to understand the defect associated with variant BDNF and provide a framework, based on divergent presynaptic regulation of sorting to Secretory Pathways, to explain how two ligands for tropomyosin-related kinase B, BDNF and NT-4, can mediate diverse biological responses.
H.-h. Gerdes - One of the best experts on this subject based on the ideXlab platform.
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Membrane traffic in the Secretory Pathway
Cellular and Molecular Life Sciences, 2008Co-Authors: H.-h. GerdesAbstract:During the last 20 years remarkable achievements have been made in the understanding of the molecular basis of membrane traffic in the Secretory Pathway. A combination of morphological, biochemical and genetical approaches revealed the identity of various compartments and transport intermediates, and provided basic functional insights into membrane trafficking. Recently, live cell imaging approaches further refined our understanding of the underlying mechanisms of budding, transport and fusion of transport containers, led to the discovery of new Pathways and triggered new concepts as to how membrane traffic is orchestrated. This multi-author review highlights recent advances in membrane traffic by focusing on transport vesicles as the central mediators of communication in the Secretory Pathway. (Part of a Multi-author Review)
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Membrane traffic in the Secretory Pathway.
Cellular and Molecular Life Sciences, 2008Co-Authors: H.-h. GerdesAbstract:During the last 20 years remarkable achievements have been made in the understanding of the molecular basis of membrane traffic in the Secretory Pathway. A combination of morphological, biochemical and genetical approaches revealed the identity of various compartments and transport intermediates, and provided basic functional insights into membrane trafficking. Recently, live cell imaging approaches further refined our understanding of the underlying mechanisms of budding, transport and fusion of transport containers, led to the discovery of new Pathways and triggered new concepts as to how membrane traffic is orchestrated. This multi-author review highlights recent advances in membrane traffic by focusing on transport vesicles as the central mediators of communication in the Secretory Pathway.
