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The core machinery for vesicular membrane trafficking broadly comprises of coat proteins, RABs, tethering complexes and SNAREs. As cellular membrane traffic modulates key processes of mitogenic signaling, cell migration, cell death and autophagy, its dysregulation could potentially results in increased cell proliferation and survival, or enhanced migration and invasion. Changes in the levels of some components of the core machinery of vesicular membrane trafficking, likely due to gene amplifications and/or alterations in epigenetic factors (such as DNA methylation and micro RNA) have been extensively associated with human cancers. Here, we provide an overview of association of membrane trafficking with cancer, with a focus on mutations and variants of coat proteins, RABs, tethering complex components and SNAREs that have been uncovered in human cancer cells/tissues. The major cellular and molecular cancer-driving or suppression mechanisms associated with these components of the core membrane trafficking machinery shall be discussed.

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Fragmented or otherwise miniaturized plastic materials in the form of micro- or nanoplastics have been of nagging environmental concern. Perturbation of organismal physiology and behavior by micro- and nanoplastics have been widely documented for marine invertebrates. Some of these effects are also manifested by larger marine vertebrates such as fishes. More recently, possible effects of micro- and nanoplastics on mammalian gut microbiota as well as host cellular and metabolic toxicity have been reported in mouse models. Human exposure to micro- and nanoplastics occurs largely through ingestion, as these are found in food or derived from food packaging, but also in a less well-defined manner though inhalation. The pathophysiological consequences of acute and chronic micro- and nanoplastics exposure in the mammalian system, particularly humans, are yet unclear. In this review, we focus on the recent findings related to the potential toxicity and detrimental effects of micro- and nanoplastics as demonstrated in mouse models as well as human cell lines. The prevailing data suggest that micro- and nanoplastics accumulation in mammalian and human tissues would likely have negative, yet unclear long-term consequences. There is a need for cellular and systemic toxicity due to micro- and nanoplastics to be better illuminated, and the underlying mechanisms defined by further work.

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Membrane trafficking processes are presumably vital for axonal regeneration after injury, but mechanistic understanding in this regard has been sparse. A recent loss-of-function screen had been carried out for factors important for axonal regeneration by cultured cortical neurons and the results suggested that the activity of a number of Rab GTPases might act to restrict axonal regeneration. A loss of Rab27b, in particular, is shown to enhance axonal regeneration in vitro, as well as in C. elegans and mouse central nervous system injury models in vivo. Possible mechanisms underlying this new finding, which has important academic and translational implication, are discussed.

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Formation of the autolysosome involves SNARE-mediated autophagosome-lysosome fusion, which is mediated by a combination of the Qa SNARE STX17 (syntaxin 17), the Qbc SNARE SNAP29 and the R-SNAREs VAMP7/8. 2 very recent reports have now implicated another R-SNARE with a longin domain, YKT6, in this fusion process. Interestingly, these reports painted two different pictures of YKT6's involvement. Studies in HeLa cells indicated that YKT6, acting independently of STX17, could form a separate SNARE complex with SNAP29 and another Qa SNARE to mediate autophagosome-lysosome fusion. Conversely, work in Drosophila larvae fat cells showed that while Ykt6 could form a SNARE complex with Snap29 and Syx17/Stx17, it is readily outcompeted by lysosomal Vamp7 in this regard. Moreover, its activity in autophagosome-lysosome fusion is not impaired by mutation of the supposedly critical ionic zero-layer residue from R to Q. In this regard, YKT6 may therefore act in a noncanonical way to regulate fusion. Here, we ponder on the fresh mechanistic perspectives on the final membrane fusion step of macroautophagy/autophagy offered by these new findings. Further, we propose another possible mechanism as to how YKT6 might act, which may provide some reconciliation to the differences observed. Abbreviations: LD: longin domain.

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Mitochondria⁻nucleus (mitonuclear) retrograde signaling via nuclear import of otherwise mitochondrial targeted factors occurs during mitochondrial unfolded protein response (UPRmt), a mechanism that counters mitochondrial and cellular stresses. Other than nuclear encoded proteins, mitochondrial DNA (mtDNA)-encoded peptides, such as humanin, are known to have important pro-survival and metabolic regulatory functions. A recent report has indicated that another mtDNA-encoded peptide, the mitochondrial open reading frame of the 12S rRNA-c (MOTS-c), could translocate into the nucleus upon stress induction. In the nucleus, MOTS-c binds to DNA and regulates the transcription of stress response genes in concert with other transcription factors. This is the first clear example of a mitochondria-derived peptide (MDP) acting in the nucleus to affect transcriptional responses to stress. Thus, MOTS-c may bear some characteristics of a 'mitokine' factor that mediates mitohormesis, influencing cell survival as well as organismal health and longevity.