Sorting and Signaling at the Golgi Complex
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We used multiple approaches to investigate the coordination of trans and medial Rab proteins in the regulation of intra-Golgi retrograde trafficking. We reasoned that medially located Rab33b might act downstream of the trans Golgi Rab, Rab6, in regulating intra-Golgi retrograde trafficking. We found that knockdown of Rab33b, like Rab6, suppressed conserved oligomeric Golgi (COG) complex- or Zeste White 10 (ZW10)-depletion induced disruption of the Golgi ribbon in HeLa cells. Moreover, efficient GTP-restricted Rab6 induced relocation of Golgi enzymes to the endoplasmic reticulum (ER) was Rab33b-dependent, but not vice versa, suggesting that the two Rabs act sequentially in an intra-Golgi Rab cascade. In support of this hypothesis, we found that overexpression of GTP-Rab33b induced the dissociation of Rab6 from Golgi membranes in vivo. In addition, the transport of Shiga-like toxin B fragment (SLTB) from the trans to cis Golgi and ER required Rab33b. Surprisingly, depletion of Rab33b had little, if any, immediate effect on cell growth and multiplication. Furthermore, anterograde trafficking of tsO45G protein through the Golgi apparatus was normal. We suggest that the Rab33b/Rab6 regulated intra-Golgi retrograde trafficking pathway must coexist with other Golgi trafficking pathways. In conclusion, we provide the first evidence that Rab33b and Rab6 act to coordinate a major intra-Golgi retrograde trafficking pathway. This coordination may have parallels with Rab conversion/cascade events that regulate endosome, phagosome and exocytic processes.
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Journal Article Dinucleotide repeat polymorphisms at the D5S257 and D5S268 loci on chromosome 5p Get access L.E. Bernard, L.E. Bernard Department of Medical Genetics, 6174 University Boulevard, University of British ColumbiaVancouver, BCV6T1Z3, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar C.N. Kreklywich, C.N. Kreklywich Department of Medical Genetics, 6174 University Boulevard, University of British ColumbiaVancouver, BCV6T1Z3, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar S. Wood S. Wood Department of Medical Genetics, 6174 University Boulevard, University of British ColumbiaVancouver, BCV6T1Z3, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 19, Issue 20, 25 October 1991, Page 5794, https://doi.org/10.1093/nar/19.20.5794 Published: 25 October 1991
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Abstract Intracellular organelles support cellular physiology in diverse conditions. In the skin, epidermal keratinocytes undergo differentiation with gradual changes in cellular physiology, accompanying remodeling in lysosomes and the Golgi apparatus. However, the functional significance and the molecular link between lysosome and Golgi remodeling were unknown. Here, we show that in differentiated keratinocytes, the Golgi apparatus redistributes as ministacks leading to a significant increase in total protein secretion. The Golgi ministacks establish contact with lysosomes facilitated by Golgi tethering protein GRASP65, the depletion of which is associated with the loss of Golgi-lysosome contact and malformation of lysosomes defined by their aberrant morphology, size, and function. Strikingly, these lysosomes receive secretory Golgi cargoes, contribute to the protein secretion from the Golgi, and are critically maintained by the secretory function of the Golgi apparatus. We uncovered a novel mechanism of lysosome specialization through unique Golgi-lysosome contact that likely supports high secretion from differentiated keratinocytes. Key points Calcium induced differentiation of human keratinocytes accompanies the dispersal of functional Golgi stacks and lysosomes. Dispersed Golgi stacks establish contact/physical apposition with the lysosomes. Golgi tether GRASP65 surrounds keratinocyte lysosomes and facilitates Golgi-lysosome apposition. GRASP65 depletion abolishes Golgi-lysosome apposition and accumulates morphologically altered non-degradative lysosomes. Lysosomes of differentiated keratinocytes receive secretory Golgi cargo and contribute to the protein secretion from the Golgi. Specialized lysosomes are maintained by the secretory function of the Golgi apparatus.
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The Golgi apparatus is an essential organelle of the secretory pathway in eukaryotic cells. It processes secretory and transmembrane proteins and orchestrates their transport to other endomembrane compartments or the plasma membrane. The Golgi apparatus thereby shapes the cell surface, controlling cell polarity, cell-cell communication, and immune signaling. The cytosolic face of the Golgi hosts and regulates signaling cascades, impacting most notably the DNA damage response and mitosis. These essential functions strongly depend on Golgi protein homeostasis and Golgi integrity. Golgi fragmentation and consequent malfunction is associated with neurodegenerative diseases and certain cancer types. Recent studies provide first insight into the critical role of ubiquitin signaling in maintaining Golgi integrity and in Golgi protein quality control. Similar to well described pathways at the endoplasmic reticulum, ubiquitin-dependent degradation of non-native proteins prevents the accumulation of toxic protein aggregates at the Golgi. Moreover, ubiquitination regulates Golgi structural rearrangements in response to cellular stress. Advances in elucidating ubiquitination and degradation events at the Golgi are starting to paint a picture of the molecular machinery underlying Golgi (protein) homeostasis.
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The Golgi apparatus has long been suggested to be important for directing secretion to specific sites on the plasma membrane in response to extracellular signaling events. However, the mechanisms by which signaling events are coordinated with Golgi apparatus function remain poorly understood. Here, we identify a scaffolding function for the Golgi matrix protein GM130 that sheds light on how such signaling events may be regulated. We show that the mammalian Ste20 kinases YSK1 and MST4 target to the Golgi apparatus via the Golgi matrix protein GM130. In addition, GM130 binding activates these kinases by promoting autophosphorylation of a conserved threonine within the T-loop. Interference with YSK1 function perturbs perinuclear Golgi organization, cell migration, and invasion into type I collagen. A biochemical screen identifies 14-3-3ζ as a specific substrate for YSK1 that localizes to the Golgi apparatus, and potentially links YSK1 signaling at the Golgi apparatus with protein transport events, cell adhesion, and polarity complexes important for cell migration.
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As an important organelle inside a cell, golgi apparatus is involved in the physiological activities like the processing and modiifcation of proteins, metabolism of lipids and vesicular transportation. Besides, it plays an important role in the ion homeostasis and stresses. In oxidative stress, the golgi apparatus undergoes the golgi apparatus stress (GA stress). hTerefore, the Ca2+/Mn2+ pump activities will alter and GA Ca2+/Mn2+ dyshomeostasis will occur functionally. Structurally, the golgi apparatus will fragment and release the stress-induced fragmentation products. Behavior mentioned above will initiate the relevant apoptotic pathway of the golgi apparatus which mediates its apoptosis. p115 (golgi-vesicular transport protein) is a stress-associated protein; fragments derived from the p115 will exert the apoptosis-inducing effects by inducing the phosphorylation of p53 in oxidative stress.
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Arabidopsis DNA hypomethylation mutation, ddm1 , results in a variety of developmental abnormalities by slowly inducing heritable lesions at unlinked loci. Here, late‐flowering traits observed at high frequencies in independently‐established ddm1 lines were genetically characterized. In all of the four late‐flowering lines examined the traits were dominant and mapped to the same chromosomal region, which is close or possibly identical to the FWA locus. The ddm1 ‐induced phenotypic onsets are apparently not random mutation events, but specific to a group of genes, suggesting the underlying epigenetic mechanism. The DNA methylation mutant provide useful system for identifying epigenetically‐regulated genes important for plant development.
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