RET-independent signaling by GDNF ligands and GFRα receptors.
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TLDR
This review summarizes the current understanding of how the best studied RET-independent signaling pathway for GDNF family ligands and GFRα receptors involves the neural cell adhesion molecule NCAM and its association with GFR α co-receptors.Abstract:
The discovery in the late 1990s of the partnership between the RET receptor tyrosine kinase and the GFRα family of GPI-anchored co-receptors as mediators of the effects of GDNF family ligands galvanized the field of neurotrophic factors, firmly establishing a new molecular framework besides the ubiquitous neurotrophins. Soon after, however, it was realized that many neurons and brain areas expressed GFRα receptors without expressing RET. These observations led to the formulation of two new concepts in GDNF family signaling, namely, the non-cell-autonomous functions of GFRα molecules, so-called trans signaling, as well as cell-autonomous functions mediated by signaling receptors distinct from RET, which became known as RET-independent signaling. To date, the best studied RET-independent signaling pathway for GDNF family ligands involves the neural cell adhesion molecule NCAM and its association with GFRα co-receptors. Among the many functions attributed to this signaling system are neuronal migration, neurite outgrowth, dendrite branching, spine formation, and synaptogenesis. This review summarizes our current understanding of this and other mechanisms of RET-independent signaling by GDNF family ligands and GFRα receptors, as well as their physiological importance.read more
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Evolutionary predictability of genetic versus nongenetic resistance to anticancer drugs in melanoma.
Oskar Marín-Béjar,Aljosja Rogiers,Michael Dewaele,Julia Femel,Panagiotis Karras,Joanna Pozniak,Greet Bervoets,Nina Van Raemdonck,Dennis Pedri,Toon Swings,Jonas Demeulemeester,Jonas Demeulemeester,Sara Vander Borght,Stefan Lehnert,Francesca Maria Bosisio,Joost van den Oord,Isabelle Vanden Bempt,Diether Lambrechts,Thierry Voet,Oliver Bechter,Helen Rizos,Mitchell P. Levesque,Eleonora Leucci,Amanda W. Lund,Florian Rambow,Jean-Christophe Marine +25 more
TL;DR: In this paper, the authors identify an approach that abrogates the nongenetic resistance trajectory in melanoma and demonstrate that the cellular composition of MRD deterministically imposes distinct drug resistance evolutionary paths.
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RET Receptor Tyrosine Kinase: Role in Neurodegeneration, Obesity, and Cancer.
Arun Kumar Mahato,Yulia Sidorova +1 more
TL;DR: The physiological ligand-dependent activation of RET receptor is important for the survival and maintenance of several neuronal populations, appetite, and weight gain control, thus providing an opportunity for the development of disease-modifying therapeutics against neurodegeneration and obesity.
Journal ArticleDOI
Long-term exposure to GDNF induces dephosphorylation of Ret, AKT, and ERK1/2, and is ineffective at protecting midbrain dopaminergic neurons in cellular models of Parkinson's disease.
V. Mesa-Infante,Domingo Afonso-Oramas,Josmar Salas-Hernández,Julia Rodriguez-Nuñez,Pedro Barroso-Chinea +4 more
TL;DR: In this paper, the authors investigated Ret activation and its effect over both signaling pathways in midbrain cell cultures treated with Glial cell line-derived neurotrophic factor (GDNF) at different doses (0.3, 1, and 10
Journal ArticleDOI
Long-term exposure to GDNF induces dephosphorylation of Ret, AKT, and ERK1/2, and is ineffective at protecting midbrain dopaminergic neurons in cellular models of Parkinson's disease
TL;DR: In this paper , the authors investigated Ret activation and its effect over both signaling pathways in midbrain cell cultures treated with GDNF at different doses (0.3, 1, and 10 ng/ml) and times (15 min, 24 h, 24 24 h (7 days), and 7 continuous days).
Journal ArticleDOI
Fasudil enhances the phagocytosis of myelin debris and the expression of neurotrophic factors in cuprizone-induced demyelinating mice.
Zhi-Bin Ding,Qing-Xian Han,Qing Wang,Li-Juan Song,Guo-Guo Chu,Minfang Guo,Zhi Chai,Jie-Zhong Yu,Bao-Guo Xiao,Xin-Yi Li,Cun-Gen Ma,Cun-Gen Ma,Cun-Gen Ma +12 more
TL;DR: Fasudil upregulated the TREM2/DAP12 pathway, which positively regulated the phagocytosis of myelin debris by microglia, and increased the expression of brain derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic Factor (GDNF) as discussed by the authors.
References
More filters
Journal ArticleDOI
Lipid rafts and signal transduction
Kai Simons,Derek Toomre +1 more
TL;DR: It is now becoming clear that lipid micro-environments on the cell surface — known as lipid rafts — also take part in this process of signalling transduction, where protein–protein interactions result in the activation of signalling cascades.
The spandrels of San Marco and the Panglossian paradigm: a critique of the adaptationist programme
TL;DR: The adaptationist programme is faulted for its failure to distinguish current utility from reasons for origin, and Darwin’s own pluralistic approach to identifying the agents of evolutionary change is supported.
Journal ArticleDOI
The spandrels of San Marco and the Panglossian paradigm: a critique of the adaptationist programme
TL;DR: In this paper, the authors criticise the adaptationist program for its inability to distinguish current utility from reasons for origin (male tyrannosaurs may have used their diminutive front legs to titillate female partners, but this will not explain why they got so small).
Journal ArticleDOI
GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons
TL;DR: In embryonic midbrain cultures, recombinant human GDNF promoted the survival and morphological differentiation of dopaminergic neurons and increased their high-affinity dopamine uptake and did not increase total neuron or astrocyte numbers or transmitter uptake.
Journal ArticleDOI
Functions of lipid rafts in biological membranes.
Deborah A. Brown,Erwin London +1 more
TL;DR: The relationship between detergent-resistant membranes, rafts, caveolae, and low-density plasma membrane fragments, and possible functions of lipid rafts in membranes are discussed.