Neuronal functions of ESCRTs

Department of Biotechnology, College of Life Science and Nano Technology, Hannam University, Dajeon 305-811, Korea.
Experimental neurobiology 03/2012; 21(1):9-15. DOI: 10.5607/en.2012.21.1.9
Source: PubMed


The endosomal sorting complexes required for transport (ESCRTs) regulate protein trafficking from endosomes to lysosomes. Recent studies have shown that ESCRTs are involved in various cellular processes, including membrane scission, microRNA function, viral budding, and the autophagy pathway in many tissues, including the nervous system. Indeed, dysfunctional ESCRTs are associated with neurodegeneration. However, it remains largely elusive how ESCRTs act in post-mitotic neurons, a highly specialized cell type that requires dynamic changes in neuronal structures and signaling for proper function. This review focuses on our current understandings of the functions of ESCRTs in neuronal morphology, synaptic plasticity, and neurodegenerative diseases.

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    • "We also observed that two members of electron transport proteins (ATP5D, NDUFS3) were enriched in the neural cells. The association of vacuolar protein sorting (vps) proteins with neuronal morphology, synaptic plasticity, and neurodegenerative diseases has been described previously which may suggest their possible contribution in neural differentiation (for review see [40]). Adp ribosylation factor-like protein 2 (Arl2) is a monomeric G protein which could interact with tubulin-folding cofactors and protects the tubulins from destruction [41] and has a role in the survival of neural progenitors differentiated from hESC [42] "
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    ABSTRACT: Unlabelled: Neural differentiation of human embryonic stem cells (hESCs) is a unique opportunity for in vitro analyses of neurogenesis in humans. Extrinsic cues through neural plate formation are well described in the hESCs although intracellular mechanisms underlying neural development are largely unknown. Proteome analysis of hESC differentiation to neural cells will help to further define molecular mechanisms involved in neurogenesis in humans. Using a two-dimensional differential gel electrophoresis (2D-DIGE) system, we analyzed the proteome of hESC differentiation to neurons at three stages, early neural differentiation, neural ectoderm and mature neurons. Out of 137 differentially accumulated protein spots, 118 spots were identified using MALDI-TOF/TOF and LC MS/MS. We observed that proteins involved in redox hemostasis, vitamin and energy metabolism and ubiquitin dependent proteolysis were more abundant in differentiated cells, whereas the abundance of proteins associated with RNA processing and protein folding was higher in hESCs. Higher abundance of proteins involved in maintaining cellular redox state suggests the importance of redox hemostasis in neural differentiation. Furthermore, our results support the concept of a coupling mechanism between neuronal activity and glucose utilization. The protein network analysis showed that the majority of the interacting proteins were associated with the cell cycle and cellular proliferation. These results enhanced our understanding of the molecular dynamics that underlie neural commitment and differentiation. Biological significance: In highlighting the role of redox and unique metabolic properties of neuronal cells, the present findings add insight to our understanding of hESC differentiation to neurons. The abundance of fourteen proteins involved in maintaining cellular redox state, including 10 members of peroxiredoxin (Prdx) family, mainly increased during differentiation, thus highlighting a link of neural differentiation to redox. Our results revealed markedly higher expression of genes encoding enzymes involved in the glycolysis and amino acid synthesis during differentiation. Protein network analysis predicted a number of critical mediators in hESC differentiation. These proteins included TP53, CTNNB1, SMARCA4, TNF, TERT, E2F1, MYC, RB1, and AR.
    Journal of proteomics 02/2014; 101. DOI:10.1016/j.jprot.2014.02.002 · 3.89 Impact Factor
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    • "After completion of autophagosome formation, autophagosomes can fuse with endosomes or lysosomes. Although it is unclear how exactly autophagosomes fuse with lysosomes, their fusion is known to require several proteins such as LAMP2, the Rubicon-UVRAG complex, SNAREs (soluble N-ethylmalemide sensitive factor attachment protein receptor), HOPS (homotypic fusion and protein sorting), Rab (Ras [rat sarcoma] like in rat brain), ESCRT (Endosormal sorting complex required for transport), and LC3 [4, 10, 11]. Once the autophagosome fuses with lysosomes, cytosolic components are degraded by hydrolases and lipases. "
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    09/2013; 22(3):133-142. DOI:10.5607/en.2013.22.3.133
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