The Golgi Apparatus: Panel Point of Cytosolic Ca<sup>2+</sup>Regulation

Li, Lihua; Tian, Xiangrong; Jiang, Zheng; Zeng, Lei; He, Wenfang; Hu, Zhiping

doi:10.1159/000350471

Cited by 15 publications

(8 citation statements)

References 122 publications

(189 reference statements)

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“…Since the level of cell activity has been directly related to the size of the GA (Lucassen et al, 1993, Salehi et al, 1995), the alterations of the GA observed in the present study would likely result in a deregulation of neuronal calcium levels (Li et al, 2013) and alterations in protein synthesis, modification, and sorting (Salehi et al, 1995, Wang et al, 2008, Xiang et al, 2013). This suggests that the defects in the GA are likely to contribute to the neurotoxicity associated with AD.…”

Section: Discussionmentioning

confidence: 79%

Morphometric alterations of Golgi apparatus in Alzheimer's disease are related to tau hyperphosphorylation

Antón-Fernández

Aparicio-Torres

Tapia

et al. 2017

Neurobiology of Disease

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The Golgi apparatus (GA) is a highly dynamic organelle, which is mainly involved in the post-translational processing and targeting of cellular proteins and which undergoes significant morphological changes in response to different physiological and pathological conditions. In the present study, we have analyzed the possible alterations of GA in neurons from the temporal neocortex and hippocampus of Alzheimer's disease (AD) patients, using double immunofluorescence techniques, confocal microscopy and 3D quantification techniques. We found that in AD patients, the percentage of temporal neocortical and CA1 hippocampal pyramidal neurons with a highly altered GA is much higher (approximately 65%) in neurons with neurofibrillary tangles (NFT) than in NFT-free neurons (approximately 6%). Quantitative analysis of the surface area and volume of GA elements in neurons revealed that, compared with NFT-free neurons, NFT-bearing neurons had a reduction of approximately one half in neocortical neurons and one third in CA1 neurons. In both regions, neurons with a pre-tangle stage of phospho-tau accumulation had surface area and GA volume values that were intermediate, that is, between those of NFT-free and NFT-bearing neurons. These findings support the idea that the progressive accumulation of phospho-tau is associated with structural alterations of the GA including fragmentation and a decrease in the surface area and volume of GA elements. These alterations likely impact the processing and trafficking of proteins, which might contribute to neuronal dysfunction in AD.

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Section: Discussionmentioning

confidence: 79%

Morphometric alterations of Golgi apparatus in Alzheimer's disease are related to tau hyperphosphorylation

Antón-Fernández

Aparicio-Torres

Tapia

et al. 2017

Neurobiology of Disease

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“…S3). The signaling lipid PI(4,5)P 2 has previously been detected on mitochondria (59), although at a much lower concentration than on the plasma membrane and in a sequestered form (59)(60)(61). We are not aware of any report showing PI4P on mitochondria.…”

Section: +mentioning

confidence: 79%

Investigations of human myosin VI targeting using optogenetically controlled cargo loading

French

Sosnick

Rock

2017

Proc. Natl. Acad. Sci. U.S.A.

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Myosins play countless critical roles in the cell, each requiring it to be activated at a specific location and time. To control myosin VI with this specificity, we created an optogenetic tool for activating myosin VI by fusing the light-sensitive Avena sativa phototropin1 LOV2 domain to a peptide from Dab2 (LOVDab), a myosin VI cargo protein. Our approach harnesses the native targeting and activation mechanism of myosin VI, allowing direct inferences on myosin VI function. LOVDab robustly recruits human full-length myosin VI to various organelles in vivo and hinders peroxisome motion in a lightcontrollable manner. LOVDab also activates myosin VI in an in vitro gliding filament assay. Our data suggest that protein and lipid cargoes cooperate to activate myosin VI, allowing myosin VI to integrate Ca 2+, lipid, and protein cargo signals in the cell to deploy in a site-specific manner.otor proteins play countless roles in biology, each requiring the motor to be recruited and activated at a particular time and place inside the cell. To dissect these multiple roles, we must develop tools that allow us to control the recruitment and activation process. One promising technique for achieving this goal is through optogenetics (1). Optogenetics involves the engineering and application of optically controlled, genetically encoded proteins and is transforming the fields of neuro-and cell biology (2, 3). A major benefit of optogenetics is that proteins are activated using light, which allows for high temporal and spatial control over a protein of interest.Myosin VI is a motor protein whose study could particularly benefit from optogenetic control. It is the only myosin known to walk toward the pointed end of actin filaments (4, 5). This property enables it to perform a diverse array of cellular functions, including cell division, endosome trafficking, autophagy, and Golgi and plasma membrane anchoring (6-9). Myosin VI is also autoinhibited, a property that is commonly found in other myosins (10). When myosin VI binds to cargo through specialized adaptor proteins, this autoinhibition is relieved through a poorly understood mechanism likely involving the disruption of an interaction between its cargo binding domain (CBD) and the myosin head (11,12). Dissociation of the CBD from the head both frees the head to bind tightly to actin and exposes dimerization sites throughout the tail domain of myosin VI, allowing it to become a processive dimer (13-15). In some cases, myosin VI could conceivably function as a monomer, for example when fulfilling its role as a membrane tether during spermatid individualization (16). If this is the case, more work is needed to elucidate the cellular signals that determine its oligomeric state at each site of action.Myosin VI has two classes of cargo proteins that bind to distinct, conserved motifs on the myosin VI C terminus (17). Disabled2, or Dab2, belongs to the class of cargo proteins that bind to a conserved WWY site on myosin (18). Optineurin (OPTN) is a member of the second class that binds ...

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“…HHD, Hailey-Hailey disease; iTRAQ, isobaric tags for relative and absolute quantitation incorrect arrangement of intercellular adhesion molecules. 29,30 Histologically, there is impaired keratinocyte adhesion as demonstrated by acantholysis. Recent research has demonstrated that at the immunohistochemical level, there is a disassociation of the intra-and extracellular domains of epidermal keratinocyte desmosomal cadherin and E-cadherin.…”

Section: Discussionmentioning

confidence: 99%

Altered levels of focal adhesion and extracellular matrix‐receptor interacting proteins were identified in Hailey‐Hailey disease by quantitative iTRAQ proteome analysis

Zhang

Jia

et al. 2018

J of Cellular Biochemistry

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Benign chronic familial pemphigus or Hailey-Hailey disease (HHD, OMIM 169600) is a rare, autosomal dominant blistering skin disorder characterized by suprabasal cell separation (acantholysis) of the epidermis. To date, the proteomic changes in skin lesions from HHD patients has not been reported yet. In this study, a sample of skin lesions from HHD patients was collected for isobaric tags for relative and absolute quantitation to analyze proteome changes compared with unaffected individuals. The 134 differentially expressed proteins were assigned to at least one Gene Ontology term, and 123 annotated proteins with significant matches were assigned to 187 known metabolic or signaling pathways listed in the Kyoto Encyclopedia of Genes and Genomes. Most of the altered proteins in skin lesions of HHD patients were enriched in pathways involved in the PI3K-Akt signaling, focal adhesion, extracellular matrix (ECM)-receptor interaction, and protein digestion and absorption, such as collagen family members, microfibril-associated glycoprotein 4 and plakophilin. The changes of proteins related to cell adhesion, ECM-receptor interaction, and protein folding and glycosylation suggested that strategy targeted to alter cell junction and extracellular microenvironment might provide a potential treatment for HHD.

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The Golgi Apparatus: Panel Point of Cytosolic Ca²⁺Regulation

Cited by 15 publications

References 122 publications

Morphometric alterations of Golgi apparatus in Alzheimer's disease are related to tau hyperphosphorylation

Morphometric alterations of Golgi apparatus in Alzheimer's disease are related to tau hyperphosphorylation

Investigations of human myosin VI targeting using optogenetically controlled cargo loading

Altered levels of focal adhesion and extracellular matrix‐receptor interacting proteins were identified in Hailey‐Hailey disease by quantitative iTRAQ proteome analysis

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The Golgi Apparatus: Panel Point of Cytosolic Ca2+Regulation

Cited by 15 publications

References 122 publications

Morphometric alterations of Golgi apparatus in Alzheimer's disease are related to tau hyperphosphorylation

Morphometric alterations of Golgi apparatus in Alzheimer's disease are related to tau hyperphosphorylation

Investigations of human myosin VI targeting using optogenetically controlled cargo loading

Altered levels of focal adhesion and extracellular matrix‐receptor interacting proteins were identified in Hailey‐Hailey disease by quantitative iTRAQ proteome analysis

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The Golgi Apparatus: Panel Point of Cytosolic Ca²⁺Regulation