Calnexin controls TrkB cell surface transport and ER-phagy in mouse cerebral cortex development

Lüningschrör, Patrick; Andreska, Thomas; Veh, Alexander; Wolf, Daniel H.; Giridhar, Neha Jadhav; Moradi, Mehri; Denzel, Angela; Sendtner, Michael

doi:10.1016/j.devcel.2023.07.004

Cited by 5 publications

(1 citation statement)

References 45 publications

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“…In order to be accessible for activation through BDNF and subsequent phosphorylation, TrkB needs to be present at the postsynaptic site in striatal SPNs. Previous work has shown that TrkB is rapidly recruited from intracellular stores to the plasma membrane when cAMP levels are rising [56][57][58][59][60]. Thus, the number of TrkB receptors present on the cell surface of dendritic spines in DRD1expressing dSPNs is dependent on DA inputs and on the activation of the D1 receptor [61].…”

Section: Introductionmentioning

confidence: 98%

Dopaminergic Input Regulates the Sensitivity of Indirect Pathway Striatal Spiny Neurons to Brain-Derived Neurotrophic Factor

Ayon-Olivas,

Wolf,

Andreska

et al. 2023

Biology

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Motor dysfunction in Parkinson’s disease (PD) is closely linked to the dopaminergic depletion of striatal neurons and altered synaptic plasticity at corticostriatal synapses. Dopamine receptor D1 (DRD1) stimulation is a crucial step in the formation of long-term potentiation (LTP), whereas dopamine receptor D2 (DRD2) stimulation is needed for the formation of long-term depression (LTD) in striatal spiny projection neurons (SPNs). Tropomyosin receptor kinase B (TrkB) and its ligand brain-derived neurotrophic factor (BDNF) are centrally involved in plasticity regulation at the corticostriatal synapses. DRD1 activation enhances TrkB’s sensitivity for BDNF in direct pathway spiny projection neurons (dSPNs). In this study, we showed that the activation of DRD2 in cultured striatal indirect pathway spiny projection neurons (iSPNs) and cholinergic interneurons causes the retraction of TrkB from the plasma membrane. This provides an explanation for the opposing synaptic plasticity changes observed upon DRD1 or DRD2 stimulation. In addition, TrkB was found within intracellular structures in dSPNs and iSPNs from Pitx3−/− mice, a genetic model of PD with early onset dopaminergic depletion in the dorsolateral striatum (DLS). This dysregulated BDNF/TrkB signaling might contribute to the pathophysiology of direct and indirect pathway striatal projection neurons in PD.

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