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Golgi apparatus regulation of differentiation
Published in C. Yan Cheng, Spermatogenesis, 2018
Louis Hermo, Regiana L. Oliveira, Charles E. Smith, Catherine E. Au, John J. M. Bergeron
GRASP55 (Golgi reassembly associated protein) has been implicated in the stacking of Golgi cisternae.102–104 Its expression first appears after meiosis with Golgi immunoreactivity to steps 1–7 spermatids, and with no localization to Sertoli or Leydig cells of the testis, all of which reveal stacked Golgi cisternae.105,106 Alternative functions to those of cisternae stacking have been proposed for GRASP55, such as unconventional protein secretion and Golgi ribbon formation.107 Unlike typical lysosomes, the acrosome has to bind to the nuclear surface of spermatids and this may involve unconventional secretion pathways to accommodate this novel function for the acrosome. Of note is the fact that of all the five Golgi proteins indicated above, only GRASP55 does not become expressed again during later steps of spermiogenesis and in the forming Hermes body, where Golgi cisternae do not form a stack (Figure 1.12a).
Immune suppressive function of IL-1α release in the tumor microenvironment regulated by calpain 1
Published in OncoImmunology, 2022
Dandan Lin, Yu Mei, Lei Lei, Zuhairah Binte Hanafi, Ziqi Jin, Yonghao Liu, Yuan Song, Yinsheng Zhang, Bo Hu, Chunliang Liu, Jinhua Lu, Haiyan Liu
It remains as a fundamental scientific question how the leaderless cytokines can be actively transported out of the cells. For a long period of time, the release of IL-1α was believed as passive due to the loss of cell membrane integrity, such as necrosis or physical damage.10 However, recent evidence has implicated an active transport route for IL-1α secretion. Zhang et al. reported a universal unconventional protein secretion (UPS) route for leaderless protein, including the mature form of IL-1α, IL-1β, IL-36α, IL-36RA, IL-37, IL-38, etc. They revealed that HSP90A binds and unfolds leaderless proteins, then interacts with the TMED10, resulting in the oligomerization of TMED10 to form a protein channel that translocates the leaderless protein into the lumen of the ER-Golgi intermediate compartment (ERGIC) for subsequent secretion out of the cell via a vesicular intermediate.45 Notably, they performed the experiments with mature form of IL-1α, whether this UPS could also transport the full-length IL-1α is unknown. More recently, Tsuchiya et al. discovered a new secretion route for IL-1α.46 They found that IL-1α maturation resulted in more IL-1α release from macrophages upon GSDMD-mediated pore formation. These findings suggested mature IL-1α might be the dominant form that could be actively transported compared with the pro-IL-1α. However, we cannot exclude the possibility that pro-IL-1α could also be actively transported out of the cell via an unknown route. Further studies are needed to address this question.
The secrets of protein secretion: what are the key features of comparative secretomics?
Published in Expert Review of Proteomics, 2020
Comparative secretomics provides unbiased access to the otherwise neglected unconventionally secreted proteins, without prior in-depth functional validation. With the help of comparative secretomics, it was possible to increase the number of candidate proteins that are secreted that lack a signal peptide and to develop a novel prediction tool for protein secretion [13]. In contrast, existing computational tools for predicting unconventional protein secretion, such as SecretomeP [14] and SPRED [15], make use of classical secretory proteins by removing their signal peptides, based on the hypothesis that all secretory proteins share common features, regardless of specific pathways [13]. In the first version, it was shown that OutCyte exhibits a higher accuracy for the prediction of unconventionally secreted proteins (AUC = 0.801). In line with this, eight features were extracted as important for the prediction of unconventional protein secretion, including a high frequency of arginine residues and positively charged amino acids. These examples verified that comparative secretomics provides a better understanding of unconventional non-vesicle-mediated secretory pathways.
Skin proteomics – analysis of the extracellular matrix in health and disease
Published in Expert Review of Proteomics, 2020
Jörn Dengjel, Leena Bruckner-Tuderman, Alexander Nyström
Next to metabolic labeling, chemical labeling was employed to follow skin proteome dynamics in an unbiased fashion. The most widely used chemical tags are isobaric tags for relative and absolute quantitation (iTRAQ) [118] and tandem mass tags (TMT) [119]. As the tags are isobaric, sample complexity is not increased and quantification is performed on the MS/MS level compared to MS-based quantification of metabolic labeling strategies. Compared to the latter, isobaric chemical tags allow a higher degree of multiplexing [120]. Depending on the product up to 16 samples may be compared in a single analysis. iTRAQ labeling was used to study unconventional protein secretion of keratinocytes in response to UVB irradiation [121]. The authors could show that UVB-activated caspase-1 plays a general role in unconventional protein secretion. By comparing secretomes of cells treated with the caspase-1 inhibitor YVAD with those of non-treated cells, 77 proteins were identified that were likely secreted in a caspase-1 activity-dependent manner. iTRAQ labeling in combination with skin fibroblasts was used to investigate possible side-effects of the HDAC inhibitor valproate in spinal muscular atrophy [122]. 2171 proteins were detected of which 1329 could be accurately quantified. While the majority of proteins appeared not affected by valproate treatment, collagen I, VI, and osteonectin were significantly reduced indicating potential side-effects on the ECM.