Browsing by Author "Perlson, Eran"

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    BDNF/TrkB signaling endosomes in axons coordinate CREB/mTOR activation and protein synthesis in the cell body to induce dendritic growth in cortical neurons
    (2023) Moya-Alvarado, Guillermo; Tiburcio-Felix, Reynaldo; Ibanez, Maria Raquel; Aguirre-Soto, Alejandro A.; Guerra, Miguel, V; Wu, Chengbiao; Mobley, William C.; Perlson, Eran; Bronfman, Francisca C.
    Brain-derived neurotrophic factor (BDNF) and its receptors tropomyosin kinase receptor B (TrkB) and the p75 neurotrophin receptor (p75) are the primary regulators of dendritic growth in the CNS. After being bound by BDNF, TrkB and p75 are endocytosed into endosomes and continue signaling within the cell soma, dendrites, and axons. We studied the functional role of BDNF axonal signaling in cortical neurons derived from different transgenic mice using compartmentalized cultures in microfluidic devices. We found that axonal BDNF increased dendritic growth from the neuronal cell body in a cAMP response element-binding protein (CREB)-dependent manner. These effects were dependent on axonal TrkB but not p75 activity. Dynein-dependent BDNF-TrkB-containing endosome transport was required for long-distance induction of dendritic growth. Axonal signaling endosomes increased CREB and mTOR kinase activity in the cell body, and this increase in the activity of both proteins was required for general protein translation and the expression of Arc, a plasticity-associated gene, indicating a role for BDNF-TrkB axonal signaling endosomes in coordinating the transcription and translation of genes whose products contribute to learning and memory regulation.
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    Retrograde Degenerative Signaling Mediated by the p75 Neurotrophin Receptor Requires p150Glued Deacetylation by Axonal HDAC1
    (2018) Pathak, Amrita; Stanley, Emily M.; Hickman, F. Edward; Wallace, Natalie; Brewer, Bryson; Li, Deyu; Gluska, Shani; Perlson, Eran; Fuhrmann, Sabine; Akassoglou, Katerina; Bronfman, Francisca; Casaccia, Patrizia; Burnette, Dylan T.; Carter, Bruce D.
    During development, neurons undergo apoptosis if they do not receive adequate trophic support from tissues they innervate or when detrimental factors activate the p75 neurotrophin receptor (p75NTR) at their axon ends. Trophic factor deprivation (TFD) or activation of p75NTR in distal axons results in a retrograde degenerative signal. However, the nature of this signal and the regulation of its transport are poorly understood. Here, we identify p75NTR intracellular domain (ICD) and histone deacetylase 1 (HDAC1) as part of a retrograde pro-apoptotic signal generated in response to TFD or ligand binding to p75NTR in sympathetic neurons. We report an unconventional function of HDAC1 in retrograde transport of a degenerative signal and its constitutive presence in sympathetic axons. HDAC1 deacetylates dynactin subunit p150(Glued), which enhances its interaction with dynein. These findings define p75NTR ICD as a retrograde degenerative signal and reveal p150(Glued) deacetylation as a unique mechanism regulating axonal transport.