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

Traffic ◽  
2021 ◽  
Author(s):  
Carlos O. Oueslati Morales ◽  
Attila Ignácz ◽  
Norbert Bencsik ◽  
Zsofia Sziber ◽  
Anikó Erika Rátkai ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Ampa Receptor ◽  
Hippocampal Neurons ◽  
Protein Kinase D ◽  
Receptor Endocytosis ◽  
Activity Dependent

scholarly journals Protein Kinase D promotes activity-dependent AMPA receptor endocytosis in hippocampal neurons

2020 ◽  
Author(s):  
Carlos O. Oueslati Morales ◽  
Attila Ignácz ◽  
Norbert Bencsik ◽  
Anikó Erika Rátkai ◽  
Wolfgang S. Lieb ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Protein Kinase ◽  
Hippocampal Neurons ◽  
Molecular Mechanisms ◽  
Network Activity ◽  
Protein Kinase D ◽  
Neuronal Network Activity ◽  
Early Endosomes ◽  
Ampar Trafficking ◽  
Activity Dependent

AbstractAMPA 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 co-localization with early endosomes. On a molecular level, we identify phosphorylation of the Rab5 effector protein and PKD substrate Rabaptin-5 to be required for promoting activity-dependent AMPAR endocytosis. Our results thus establish an important role for PKD in the regulation of postsynaptic AMPAR trafficking during synaptic plasticity.

scholarly journals MicroRNA-186-5p controls GluA2 surface expression and synaptic scaling in hippocampal neurons

2019 ◽  
Vol 116 (12) ◽  
pp. 5727-5736 ◽  
Author(s):  
Mariline M. Silva ◽  
Beatriz Rodrigues ◽  
Joana Fernandes ◽  
Sandra D. Santos ◽  
Laura Carreto ◽  
...  
Keyword(s):  
Ampa Receptor ◽  
Ampa Receptors ◽  
Hippocampal Neurons ◽  
Surface Expression ◽  
Receptor Expression ◽  
Synaptic Activity ◽  
Synaptic Scaling ◽  
Posttranscriptional Control ◽  
Direct Target ◽  
Activity Dependent

Homeostatic synaptic scaling is a negative feedback response to fluctuations in synaptic strength induced by developmental or learning-related processes, which maintains neuronal activity stable. Although several components of the synaptic scaling apparatus have been characterized, the intrinsic regulatory mechanisms promoting scaling remain largely unknown. MicroRNAs may contribute to posttranscriptional control of mRNAs implicated in different stages of synaptic scaling, but their role in these mechanisms is still undervalued. Here, we report that chronic blockade of glutamate receptors of the AMPA and NMDA types in hippocampal neurons in culture induces changes in the neuronal mRNA and miRNA transcriptomes, leading to synaptic upscaling. Specifically, we show that synaptic activity blockade persistently down-regulates miR-186-5p. Moreover, we describe a conserved miR-186-5p-binding site within the 3′UTR of the mRNA encoding the AMPA receptor GluA2 subunit, and demonstrate that GluA2 is a direct target of miR-186-5p. Overexpression of miR-186 decreased GluA2 surface levels, increased synaptic expression of GluA2-lacking AMPA receptors, and blocked synaptic scaling, whereas inhibition of miR-186-5p increased GluA2 surface levels and the amplitude and frequency of AMPA receptor-mediated currents, and mimicked excitatory synaptic scaling induced by synaptic inactivity. Our findings elucidate an activity-dependent miRNA-mediated mechanism for regulation of AMPA receptor expression.

scholarly journals Protein Kinase D Controls the Integrity of Golgi Apparatus and the Maintenance of Dendritic Arborization in Hippocampal Neurons

2009 ◽  
Vol 20 (7) ◽  
pp. 2108-2120 ◽  
Author(s):  
Katalin Czöndör ◽  
Kornelia Ellwanger ◽  
Yannick F. Fuchs ◽  
Sylke Lutz ◽  
Márton Gulyás ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Golgi Complex ◽  
Hippocampal Neurons ◽  
Fluorescent Protein ◽  
Dendritic Tree ◽  
Secretory Vesicle ◽  
Dendritic Arborization ◽  
Dominant Negative ◽  
Protein Kinase D ◽  
Specific Expression

Protein kinase D (PKD) is known to participate in various cellular functions, including secretory vesicle fission from the Golgi and plasma membrane-directed transport. Here, we report on expression and function of PKD in hippocampal neurons. Expression of an enhanced green fluorescent protein (EGFP)-tagged PKD activity reporter in mouse embryonal hippocampal neurons revealed high endogenous PKD activity at the Golgi complex and in the dendrites, whereas PKD activity was excluded from the axon in parallel with axonal maturation. Expression of fluorescently tagged wild-type PKD1 and constitutively active PKD1S738/742E (caPKD1) in neurons revealed that both proteins were slightly enriched at the trans-Golgi network (TGN) and did not interfere with its thread-like morphology. By contrast, expression of dominant-negative kinase inactive PKD1K612W (kdPKD1) led to the disruption of the neuronal Golgi complex, with kdPKD1 strongly localized to the TGN fragments. Similar findings were obtained from transgenic mice with inducible, neuron-specific expression of kdPKD1-EGFP. As a prominent consequence of kdPKD1 expression, the dendritic tree of transfected neurons was reduced, whereas caPKD1 increased dendritic arborization. Our results thus provide direct evidence that PKD activity is selectively involved in the maintenance of dendritic arborization and Golgi structure of hippocampal neurons.

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