-
Biomolecules Aug 2015Proteoglycans (PGs) are glycosylated proteins of biological importance at cell surfaces, in the extracellular matrix, and in the circulation. PGs are produced and... (Review)
Review
Proteoglycans (PGs) are glycosylated proteins of biological importance at cell surfaces, in the extracellular matrix, and in the circulation. PGs are produced and modified by glycosaminoglycan (GAG) chains in the secretory pathway of animal cells. The most common GAG attachment site is a serine residue followed by a glycine (-ser-gly-), from which a linker tetrasaccharide extends and may continue as a heparan sulfate, a heparin, a chondroitin sulfate, or a dermatan sulfate GAG chain. Which type of GAG chain becomes attached to the linker tetrasaccharide is influenced by the structure of the protein core, modifications occurring to the linker tetrasaccharide itself, and the biochemical environment of the Golgi apparatus, where GAG polymerization and modification by sulfation and epimerization take place. The same cell type may produce different GAG chains that vary, depending on the extent of epimerization and sulfation. However, it is not known to what extent these differences are caused by compartmental segregation of protein cores en route through the secretory pathway or by differential recruitment of modifying enzymes during synthesis of different PGs. The topic of this review is how different aspects of protein structure, cellular biochemistry, and compartmentalization may influence GAG synthesis.
Topics: Animals; Glycosaminoglycans; Golgi Apparatus; Humans; Membrane Transport Proteins; Secretory Pathway
PubMed: 26308067
DOI: 10.3390/biom5032003 -
The Journal of Cell Biology Jun 2022The mammalian Golgi comprises tightly adjacent and flattened membrane sacs called cisternae. We still do not understand the molecular organization of the Golgi and...
The mammalian Golgi comprises tightly adjacent and flattened membrane sacs called cisternae. We still do not understand the molecular organization of the Golgi and intra-Golgi transport of cargos. One of the most significant challenges to studying the Golgi is resolving Golgi proteins at the cisternal level under light microscopy. We have developed a side-averaging approach to visualize the cisternal organization and intra-Golgi transport in nocodazole-induced Golgi ministacks. Side-view images of ministacks acquired from Airyscan microscopy are transformed and aligned before intensity normalization and averaging. From side-average images of >30 Golgi proteins, we uncovered the organization of the pre-Golgi, cis, medial, trans, and trans-Golgi network membrane with an unprecedented spatial resolution. We observed the progressive transition of a synchronized cargo wave from the cis to the trans-side of the Golgi. Our data support our previous finding, in which constitutive cargos exit at the trans-Golgi while the secretory targeting to the trans-Golgi network is signal dependent.
Topics: Animals; Biological Transport; Golgi Apparatus; Mammals; Nocodazole; trans-Golgi Network
PubMed: 35467701
DOI: 10.1083/jcb.202109114 -
Tissue & Cell Apr 2017The Golgi phosphoprotein 3 (GOLPH3) is encoded by a gene that is located in a region of the human genome that is often amplified in different solid tumours. GOLPH3, an... (Review)
Review
The Golgi phosphoprotein 3 (GOLPH3) is encoded by a gene that is located in a region of the human genome that is often amplified in different solid tumours. GOLPH3, an evolutionary conserved phosphatidylinositol 4-phosphate (PI4P) binding protein, is mainly localised at trans Golgi network (TGN). It regulates several cellular functions like Golgi vesicular trafficking, Golgi glycosylation and mitochondrial cardiolipin production. Recently, GOLPH3 was discovered to be part of the DNA damage response signalling pathway, with a role in cell survival following DNA damage. In this review, we will explore the cellular functions regulated by GOLPH3 and discuss if and how they contribute to the oncogenic activity of this intriguing Golgi localized oncoprotein.
Topics: Amino Acid Sequence; Carcinogenesis; Cell Transformation, Neoplastic; DNA Damage; Golgi Apparatus; Humans; Membrane Proteins; Phosphatidylinositol Phosphates; Protein Transport; trans-Golgi Network
PubMed: 27378035
DOI: 10.1016/j.tice.2016.06.008 -
International Review of Cell and... 2015Rab proteins, small GTPases, are key regulators of mammalian Golgi apparatus organization. Based on the effect of Rab activation state, Rab proteins fall into two... (Review)
Review
Rab proteins, small GTPases, are key regulators of mammalian Golgi apparatus organization. Based on the effect of Rab activation state, Rab proteins fall into two functional classes. In Class1, inactivation induces Golgi ribbon fragmentation and/or redistribution of Golgi enzymes to the Endoplasmic Reticulum, while overexpression of wild type or activation has little, if any, effect on Golgi ribbon organization. In Class 2, the reverse is true. We give emphasis to Rab6, the most abundant Golgi-associated Rab protein. Rab6 depletion in HeLa cells causes an increase in Golgi cisternal number, longer, more continuous cisternae, and a pronounced accumulation of vesicles; the effect of Rab6 on Golgi ribbon organization is probably through regulation of vesicle transport. In effector studies, motor proteins and their regulators are found to be key Rab6 effectors. A related Rab, Rab41, affects Golgi ribbon organization in a contrasting manner. The balance between minus- and plus-end directed motor recruitment may well be the major Rab-dependent factor in Golgi ribbon organization.
Topics: Animals; Golgi Apparatus; Humans; Models, Biological; Phenotype; rab GTP-Binding Proteins
PubMed: 25708460
DOI: 10.1016/bs.ircmb.2014.12.002 -
BMB Reports May 2021The Golgi complex plays a central role in protein secretion by regulating cargo sorting and trafficking. As these processes are of functional importance to cell... (Review)
Review
The Golgi complex plays a central role in protein secretion by regulating cargo sorting and trafficking. As these processes are of functional importance to cell polarity, motility, growth, and division, there is considerable interest in achieving a comprehensive understanding of Golgi complex biology. However, the unique stack structure of this organelle has been a major hurdle to our understanding of how proteins are secreted through the Golgi apparatus. Herein, we summarize available relevant research to gain an understanding of protein secretion via the Golgi complex. This includes the molecular mechanisms of intra-Golgi trafficking and cargo export in the trans-Golgi network. Moreover, we review recent insights on signaling pathways regulated by the Golgi complex and their physiological significance. [BMB Reports 2021; 54(5): 246-252].
Topics: Golgi Apparatus; Humans; Proteins
PubMed: 33612152
DOI: 10.5483/BMBRep.2021.54.5.270 -
Methods in Molecular Biology (Clifton,... 2023The Golgi is a complex structure characterized by stacks of tightly aligned flat cisternae. In mammalian cells, Golgi stacks often concentrate in the perinuclear region...
The Golgi is a complex structure characterized by stacks of tightly aligned flat cisternae. In mammalian cells, Golgi stacks often concentrate in the perinuclear region and link together to form a ribbon. This structure is dynamic to accommodate continuous cargo flow in and out of the Golgi in both directions and undergoes morphological changes under physiological and pathological conditions. The fine, stacked Golgi structure makes it difficult to study by conventional light or even super-resolution microscopy. Furthermore, efforts to understand how Golgi structural dynamics impact cellular processes have been slow because of the knowledge gap in the protein machinery that maintains the complex and dynamic Golgi structure. In this method article, we list the common assays used in our research to help new and established researchers select the most appropriate method to properly address their questions.
Topics: Animals; Golgi Apparatus; Mammals
PubMed: 36512224
DOI: 10.1007/978-1-0716-2639-9_20 -
Plant Physiology and Biochemistry : PPB Dec 2021The organelles of the secretory pathway are characterized by specific organization and function but they communicate in different ways with intense functional crosstalk.... (Review)
Review
The organelles of the secretory pathway are characterized by specific organization and function but they communicate in different ways with intense functional crosstalk. The best known membrane-bound transport carriers are known as protein-coated vesicles. Other traffic mechanisms, despite the intense investigations, still show incongruences. The review intends to provide a general view of the mechanisms involved in membrane traffic. We evidence that organelles' biogenesis involves mechanisms that actively operate during the entire cell cycle and the persistent interconnections between the Endoplasmic reticulum (ER), Golgi apparatus, trans-Golgi network (TGN) and endosomes, the vacuolar complex and the plasma membrane (PM) may be seen as a very dynamic membrane network in which vesicular traffic is part of a general maturation process.
Topics: Cell Membrane; Endoplasmic Reticulum; Golgi Apparatus; Plant Cells; Protein Transport; trans-Golgi Network
PubMed: 34775176
DOI: 10.1016/j.plaphy.2021.11.003 -
FEBS Letters Nov 2022Formation of disulfide bonds in secreted and cell-surface proteins involves numerous enzymes and chaperones abundant in the endoplasmic reticulum (ER), the first and... (Review)
Review
Formation of disulfide bonds in secreted and cell-surface proteins involves numerous enzymes and chaperones abundant in the endoplasmic reticulum (ER), the first and main site for disulfide bonding in the secretory pathway. Although the Golgi apparatus is the major station after the ER, little is known about thiol-based redox activity in this compartment. QSOX1 and its paralog QSOX2 are the only known Golgi-resident enzymes catalyzing disulfide bonding. The localization of disulfide catalysts in an organelle downstream of the ER in the secretory pathway has long been puzzling. Recently, it has emerged that QSOX1 regulates particular glycosyltransferases, thereby influencing a central activity of the Golgi. Surprisingly, a few important disulfide-mediated multimerization events occurring in the Golgi were found to be independent of QSOX1. These multimerization events depend, however, on the low pH of the Golgi lumen and secretory granules. We compare and contrast disulfide-mediated multimerization in the ER vs. the Golgi to illustrate the variety of mechanisms controlling covalent supramolecular assembly of secreted proteins.
Topics: Golgi Apparatus; Endoplasmic Reticulum; Proteins; Oxidation-Reduction; Disulfides
PubMed: 36214053
DOI: 10.1002/1873-3468.14510 -
Cells Apr 2022The Golgi apparatus is at the center of protein processing and trafficking in normal cells. Under pathological conditions, such as in cancer, aberrant Golgi dynamics... (Review)
Review
The Golgi apparatus is at the center of protein processing and trafficking in normal cells. Under pathological conditions, such as in cancer, aberrant Golgi dynamics alter the tumor microenvironment and the immune landscape, which enhances the invasive and metastatic potential of cancer cells. Among these changes in the Golgi in cancer include altered Golgi orientation and morphology that contribute to atypical Golgi function in protein trafficking, post-translational modification, and exocytosis. Golgi-associated gene mutations are ubiquitous across most cancers and are responsible for modifying Golgi function to become pro-metastatic. The pharmacological targeting of the Golgi or its associated genes has been difficult in the clinic; thus, studying the Golgi and its role in cancer is critical to developing novel therapeutic agents that limit cancer progression and metastasis. In this review, we aim to discuss how disrupted Golgi function in cancer cells promotes invasion and metastasis.
Topics: Golgi Apparatus; Humans; Neoplasms; Protein Transport; Tumor Microenvironment
PubMed: 35563790
DOI: 10.3390/cells11091484 -
Trends in Biochemical Sciences Dec 2020It has been demonstrated that two Golgi stacking proteins, GRASP55 and GRASP65, self-interact to form trans-oligomers that tether adjacent Golgi membranes into stacks... (Review)
Review
It has been demonstrated that two Golgi stacking proteins, GRASP55 and GRASP65, self-interact to form trans-oligomers that tether adjacent Golgi membranes into stacks and ribbons in mammalian cells. This ensures proper functioning of the Golgi apparatus in protein trafficking and processing. More recently, GRASP proteins have drawn extensive attention from researchers due to their diverse and essential roles in and out of the Golgi in different organisms. In this review, we summarize their established roles in Golgi structure formation and function under physiological conditions. We then highlight the emerging and divergent roles for individual GRASP proteins, focusing on GRASP65 in cell migration and apoptosis and GRASP55 in unconventional protein secretion and autophagy under stress or pathological conditions.
Topics: Animals; Cell Movement; Golgi Apparatus; Golgi Matrix Proteins; Protein Transport
PubMed: 32893104
DOI: 10.1016/j.tibs.2020.08.001