PLC-γ-Ca2+ pathway regulates axonal TrkB endocytosis and is required for long-distance propagation of BDNF signaling

dc.contributor.authorMoya-Alvarado, Guillermo
dc.contributor.authorValero-Peña, Xavier
dc.contributor.authorAguirre-Soto, Alejandro
dc.contributor.authorBustos, Fernando J.
dc.contributor.authorLazo, Oscar M.
dc.contributor.authorBronfman, Francisca C.
dc.date.accessioned2024-05-20T18:22:09Z
dc.date.available2024-05-20T18:22:09Z
dc.date.issued2024-04-04
dc.descriptionIndexación: Scopus.
dc.description.abstractBrain-derived neurotrophic factor (BDNF) and its tropomyosin receptor kinase B (TrkB) are important signaling proteins that regulate dendritic growth and maintenance in the central nervous system (CNS). After binding of BDNF, TrkB is endocytosed into endosomes and continues signaling within the cell soma, dendrites, and axon. In previous studies, we showed that BDNF signaling initiated in axons triggers long-distance signaling, inducing dendritic arborization in a CREB-dependent manner in cell bodies, processes that depend on axonal dynein and TrkB activities. The binding of BDNF to TrkB triggers the activation of different signaling pathways, including the ERK, PLC-γ and PI3K-mTOR pathways, to induce dendritic growth and synaptic plasticity. How TrkB downstream pathways regulate long-distance signaling is unclear. Here, we studied the role of PLC-γ-Ca2+ in BDNF-induced long-distance signaling using compartmentalized microfluidic cultures. We found that dendritic branching and CREB phosphorylation induced by axonal BDNF stimulation require the activation of PLC-γ in the axons of cortical neurons. Locally, in axons, BDNF increases PLC-γ phosphorylation and induces intracellular Ca2+ waves in a PLC-γ-dependent manner. In parallel, we observed that BDNF-containing signaling endosomes transport to the cell body was dependent on PLC-γ activity and intracellular Ca2+ stores. Furthermore, the activity of PLC-γ is required for BDNF-dependent TrkB endocytosis, suggesting a role for the TrkB/PLC-γ signaling pathway in axonal signaling endosome formation.
dc.description.urihttps://www-scopus-com.recursosbiblioteca.unab.cl/record/display.uri?eid=2-s2.0-85191090892&origin=resultslist&sort=plf-f&src=s&nlo=&nlr=&nls=&sid=bec5d58e0545458a448a1e43893f93e6&sot=aff&sdt=cl&cluster=scofreetoread%2c%22all%22%2ct&sl=34&s=AF-ID%2860002636%29+AND+SUBJAREA%28NEUR%29&relpos=1&citeCnt=0&searchTerm=
dc.identifier.citationFrontiers in Molecular Neuroscience Open Access Volume 172024 Article number 1009404
dc.identifier.doi10.3389/fnmol.2024.1009404
dc.identifier.issn16625099
dc.identifier.urihttps://repositorio.unab.cl/handle/ria/56937
dc.language.isoen
dc.publisher16625099
dc.rights.licenseCC BY 4.0 DEED Attribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectaxonal transport
dc.subjectbrain-derived neurotrophic factor
dc.subjectcalcium
dc.subjectdendritic branching
dc.subjectendocytosis
dc.subjectPLC-γ
dc.subjectsignaling endosomes
dc.subjectTrkB
dc.titlePLC-γ-Ca2+ pathway regulates axonal TrkB endocytosis and is required for long-distance propagation of BDNF signaling
dc.typeArtículo
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