The MITF family of transcription factors: Role in endolysosomal biogenesis, Wnt signaling, and oncogenesis

Ploper, Diego; Robertis, Edward M. De

doi:10.1016/j.phrs.2015.04.006

Cited by 65 publications

(57 citation statements)

References 99 publications

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“…Together, this suggests that TFEB and its related transcription factors may differentially modulate different sets of genes. This is consistent with the evidence that TFEB and related factors respond to diverse physiological cues including autophagy, lysosome stress, WNT signaling, S. aureus, E. coli and IgG immune complexes [19,21,23,39]. Given this diversity of inputs, one might expect different sets of signaling pathways to combine to allow TFEB to express subsets of genes in response to a specific input.…”

Section: Discussionsupporting

confidence: 84%

Phagocytosis Enhances Lysosomal and Bactericidal Properties by Activating the Transcription Factor TFEB

et al. 2016

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Summary Macrophages internalize pathogens through phagocytosis, entrapping them into organelles called phagosomes. Phagosomes then fuse with lysosomes to mature into phagolysosomes, acquiring an acidic and hydrolytic lumen that kills the pathogens. During an ongoing infection, macrophages can internalize dozens of bacteria. Thus, we hypothesized that an initial round of phagocytosis might boost lysosome function and bactericidal ability to cope with subsequent rounds of phagocytosis. To test this hypothesis, we employed Fcγ receptor-mediated phagocytosis and endocytosis, which respectively internalize immunoglobulin G (IgG)-opsonized particles and polyvalent IgG immune complexes. We report that Fcγ receptor activation in macrophages enhanced lysosome-based proteolysis and killing of subsequently phagocytosed E. coli compared to naïve macrophages. Importantly, we show that Fcγ receptor activation caused nuclear translocation of TFEB, a transcription factor that boosts expression of lysosome genes. Indeed, Fc receptor activation was accompanied by increased expression of specific lysosomal proteins. Remarkably, TFEB silencing repressed the Fcγ receptor-mediated enhancements in degradation and bacterial killing. In addition, nuclear translocation of TFEB required phagosome completion and failed to occur in cells silenced for MCOLN1, a lysosomal Ca2+ channel, suggesting that lysosomal Ca2+ released during phagosome maturation activates TFEB. Finally, we demonstrated that non-opsonic phagocytosis of E. coli also enhanced lysosomal degradation in a TFEB-dependent manner suggesting that this phenomenon is not limited to Fcγ receptors. Overall, we show that macrophages become better killers after one round of phagocytosis and suggest that phagosomes and lysosomes are capable of bi-directional signaling.

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Section: Discussionsupporting

confidence: 84%

Phagocytosis Enhances Lysosomal and Bactericidal Properties by Activating the Transcription Factor TFEB

et al. 2016

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“…This sequestration event enables the activation of Wnt signaling for growth and differentiation (95)(96)(97). GSK-3β also plays a role in controlling the flux of endocytosis through the clathrin-coated vesicles.…”

Section: Signaling and Autophagosomesmentioning

confidence: 99%

Spatial and Temporal Regulation of Receptor Tyrosine Kinase Activation and Intracellular Signal Transduction

Bergeron

Guglielmo

Dahan

et al. 2016

Annu. Rev. Biochem.

101

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Epidermal growth factor (EGF) and insulin receptor tyrosine kinases (RTKs) exemplify how receptor location is coupled to signal transduction. Extracellular binding of ligands to these RTKs triggers their concentration into vesicles that bud off from the cell surface to generate intracellular signaling endosomes. On the exposed cytosolic surface of these endosomes, RTK autophosphorylation selects the downstream signaling proteins and lipids to effect growth factor and polypeptide hormone action. This selection is followed by the recruitment of protein tyrosine phosphatases that inactivate the RTKs and deliver them by membrane fusion and fission to late endosomes. Coincidentally, proteinases inside the endosome cleave the EGF and insulin ligands. Subsequent inward budding of the endosomal membrane generates multivesicular endosomes. Fusion with lysosomes then results in RTK degradation and downregulation. Through the spatial positioning of RTKs in target cells for EGF and insulin action, the temporal extent of signaling, attenuation, and downregulation is regulated.

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“…This network became known as the coordinated lysosomal expression and regulation (CLEAR) gene network and was characterized by the presence of the CLEAR element, a sequence proximal to the promoter of these genes to which TFEB directly binds . TFEB and the related MITF, TFE3 and TFEC transcription factors, all of which exhibit various splice variants and that can heterodimerize with each other, are thus part of a complex regulatory network that facilitates lysosome adaptation and scaling in response to a number of intrinsic and extrinsic cues …”

Section: Adaptability Of Membrane Traffic and Organellesmentioning

confidence: 99%

The big and intricate dreams of little organelles: Embracing complexity in the study of membrane traffic

Liu

Botelho

Antonescu

2017

Traffic

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Compartmentalization of eukaryotic cells into dynamic organelles that exchange material through regulated membrane traffic governs virtually every aspect of cellular physiology including signal transduction, metabolism and transcription. Much has been revealed about the molecular mechanisms that control organelle dynamics and membrane traffic and how these processes are regulated by metabolic, physical and chemical cues. From this emerges the understanding of the integration of specific organellar phenomena within complex, multiscale and nonlinear regulatory networks. In this review, we discuss systematic approaches that revealed remarkable insight into the complexity of these phenomena, including the use of proximity-based proteomics, high-throughput imaging, transcriptomics and computational modeling. We discuss how these methods offer insights to further understand molecular versatility and organelle heterogeneity, phenomena that allow a single organelle population to serve a range of physiological functions. We also detail on how transcriptional circuits drive organelle adaptation, such that organelles may shift their function to better serve distinct differentiation and stress conditions. Thus, organelle dynamics and membrane traffic are functionally heterogeneous and adaptable processes that coordinate with higher-order system behavior to optimize cell function under a range of contexts. Obtaining a comprehensive understanding of organellar phenomena will increasingly require combined use of reductionist and system-based approaches.

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The MITF family of transcription factors: Role in endolysosomal biogenesis, Wnt signaling, and oncogenesis

Cited by 65 publications

References 99 publications

Phagocytosis Enhances Lysosomal and Bactericidal Properties by Activating the Transcription Factor TFEB

Phagocytosis Enhances Lysosomal and Bactericidal Properties by Activating the Transcription Factor TFEB

Spatial and Temporal Regulation of Receptor Tyrosine Kinase Activation and Intracellular Signal Transduction

The big and intricate dreams of little organelles: Embracing complexity in the study of membrane traffic

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