Protein kinase D promotes activity‐dependent AMPA receptor endocytosis in hippocampal neurons

Abstract

α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) type glutamate receptors (AMPARs) mediate the majority of fast excitatory neurotransmission in the brain. The continuous trafficking of AMPARs into and out of synapses is a core feature of synaptic plasticity, which is considered as the cellular basis of learning and memory. The molecular mechanisms underlying the postsynaptic AMPAR trafficking, however, are still not fully understood. In this work, we demonstrate that the protein kinase D (PKD) family promotes basal and activity-induced AMPAR endocytosis in primary hippocampal neurons. Pharmacological inhibition of PKD increased synaptic levels of GluA1-containing AMPARs, slowed down their endocytic trafficking and increased neuronal network activity. By contrast, ectopic expression of constitutive active PKD decreased the synaptic level of AMPARs, while increasing their colocalization with early endosomes. Our results thus establish an important role for PKD in the regulation of postsynaptic AMPAR trafficking during synaptic plasticity.

Dendritic effects of genetically encoded actin-labeling probes in cultured hippocampal neurons

“…Embryonic hippocampal cultures were prepared from CD1 mice on embryonic day 17-18, according to Morales et al. (2021 ).…”

“…Three morphotypes were distinguished: stubby spines that were shorter than 0.8 μm, thin spines that were longer than 0.8 μm and their head/neck diameter ratios were smaller than 1.5, and mushroom spines that were longer than 0.8 μm and their head/neck diameter ratios higher than 1.5. The ratios used for morphotyping were according to Morales et al. (2021 ).…”

Membrane trafficking in breast cancer progression: protein kinase D comes into play

“…Both isoforms are further modulated in their activity by tyrosine phosphorylation and contribute to the detoxification and survival of the cell by activating various downstream signalling pathways [detailed review in ( Cobbaut and Lint, 2018 )]. PKD1 was also reported to be involved in endosomal trafficking of plasma membrane-localized receptors such as integrins and AMPA receptors, presumably through phosphorylation of the Rab5 effector protein rabaptin-5 ( Woods et al, 2004 ; Christoforides et al, 2012 ; Oueslati Morales et al, 2021 ). Consistent with this, ectopically expressed, kinase-inactive PKD1 was detected on endocytic vesicles that are downstream of a Rab4-dependent transport step ( Woods et al, 2004 ).…”