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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
During early spermiogenesis, the chromatoid body is closely associated with the Golgi apparatus. It is seen as a spongy-looking mass of electron dense granulofilamentous material with areas of low electron density infiltrated with numerous medium-sized vesicles.14,141–143 In late spermiogenesis, the chromatoid body migrates toward the centrioles occupying the opposite pole of the nucleus alongside the annulus of the flagellum.142,144 The vesicles are CMPase- and NADPase-positive, suggesting a contributing role from the Golgi apparatus.24 VPS26A/VPS35-containing retromer vesicles have also been identified within the chromatoid body.145 Some of our Golgi localized proteins during acrosome formation may also have an impact on vesicles associated with the chromatoid body.
There and back again: a dendrimer’s tale
Published in Drug and Chemical Toxicology, 2022
Barbara Ziemba, Maciej Borowiec, Ida Franiak-Pietryga
Following endocytosis, the vacuoles with dendrimer cargo become accessible to early endosomes which then fuze with late endosomes and next with lysosomes to form phagolysosomes (Šamaj et al. 2004). Dendrimers may also get to transcytotic vesicles responsible for vesicular transport through the cell and exocytosis. In another scenario, a material taken up in the CvME process may be transported via caveolosomes to the endoplasmic reticulum (ER) or the Golgi apparatus (GA) (Pérez-Martínez et al. 2011, Fröhlich 2012) (Figure 2). Wu et al. tested PAMAM dendrimers with two different end-terminal functionalities (carboxylate or pyrrolidone) in two human endothelial cell lines, i.e., hCMEC/D3 (human brain capillary endothelial cells) and HUVEC (human umbilical vein endothelial cells). Both dendrimers mainly entered the cells via CME, and after the internalization, the majority of them were found in the endo-lysosomal compartments. Some fraction of nanoparticles, however, localized to the ER and the GA. The authors excluded CvME as a significant route of dendrimers uptake and suggested the involvement of recycling endosomes trafficking to the trans-Golgi network through specialized adaptors and retromer complex (Wu et al.2017).
Status update in the use of cell-penetrating peptides for the delivery of macromolecular therapeutics
Published in Expert Opinion on Biological Therapy, 2021
Kaido Kurrikoff, Birgit Vunk, Ülo Langel
An interesting study was presented by Zhang et al, who recently developed a peptide that inhibits viral infection by looking at the human papillomavirus L2 capsid protein interactions with the retromer complex during the infection process. The authors assessed if a peptide consisting of the retromer-binding motif together with the CPP motif present in the L2 inhibit the viral entry process by acting as a retromer and L2 interacting peptide. TAT CPP motif was also assessed. Interestingly, the interacting peptide containing retromer-binding motif sequesters retromer from viral entry and inhibits the viral escape from the endosomes, inhibiting infection, the latter was also demonstrated in a mouse infection model [51]. This shows that intracellular virus trafficking is a vulnerability that can be harnessed in therapeutic purposes and retromer binding is a potential antiviral target for the HPV.
Rollercoaster ride of kynurenines: steering the wheel towards neuroprotection in Alzheimer’s disease
Published in Expert Opinion on Therapeutic Targets, 2018
Radhika Sharma, Karan Razdan, Yashika Bansal, Anurag Kuhad
There is a positive feedback loop operative in AD between inflammation and APP processing, which leads to incessant formation of Aβ. This loop hinders the termination of inflammation. Further accumulation of Aβ and various other activating factors creates a vicious circle of chronic, non-resolving inflammation. Sustained exposure to Aβ, chemokines, cytokines, and other inflammatory mediators seems to be responsible for the persistent functional impairment of microglial cells seen at plaque sites [65,66]. Aβ has been shown to induce microglial senescence, thus compromising its ability to maintain neuronal health and phagocytose amyloid plaques [67]. Constant exposure to inflammatory microenvironment negatively affects microglial function. This is corroborated by finding that stimulation of microglia with TNF-α causes downregulation of receptors for Aβ binding and degradation and reduction in phagocytosis of Aβ by microglia in vitro [68]. Beclin 1 governs the microglial functions intracellularly and works as an autophagy protein. It also functions as a part of the retromer sorting pathway, which plays a role in the recycling of transmembrane receptors such as TREM2, APP, CD36, and BACE1. Expression of Beclin 1 is found to be compromised in the brains of AD patients. This hampers the efficient phagocytic functions, which compromise the receptor recycling of CD36 and TREM2 [69].