Involvement of Cdk5 in Synaptic Plasticity, and Learning and Memory

Plattner, Florian; Giese, Karl-Peter; Angelo, Marco

doi:10.1007/978-0-387-78887-6_16

Cited by 4 publications

(6 citation statements)

References 129 publications

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“…Aak1 in turn phosphorylates AP2 subunits 2m1 and 2m2 (also both found regulated by phosphorylation in our dataset). Based on downstream substrate candidates presented here, Cdk's seem to be involved in initiation of AMPAR endocytosis, next to their known role in cytoskeleton reorganization 73,74 .…”

Section: Activated Kinases Upon Group I Mglur Stimulation With Dhpg Bmentioning

confidence: 99%

Temporal Quantitative Proteomics of mGluR-induced Protein Translation and Phosphorylation in Neurons

Gelder

Penning

Veth

et al. 2020

Molecular & Cellular Proteomics

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At neuronal synapses, activation of group I metabotropic glutamate receptors (mGluR1/5) triggers a form of long-term depression (mGluR-LTD) that relies on new protein synthesis and the internalization of AMPA-type glutamate receptors. Dysregulation of these processes has been implicated in the development of mental disorders such as autism spectrum disorders and therefore merit a better understanding on a molecular level. Here, to study mGluR-induced signaling pathways, we integrated quantitative phosphoproteomics with the analyses of newly synthesized proteins via bio-orthogonal amino acids (azidohomoalanine) in a pulsed labeling strategy in cultured hippocampal neurons stimulated with DHPG, a specific agonist for group I mGluRs. We identified several kinases with important roles in DHPG-induced mGluR activation, which we confirmed using small molecule kinase inhibitors. Furthermore, changes in the AMPA receptor endocytosis pathway in both protein synthesis and protein phosphorylation were identified, whereby Intersectin-1 was validated as a novel player in this pathway. This study revealed several new insights into the molecular pathways downstream of group I mGluR activation in hippocampal neurons, and provides a rich resource for further analyses.

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Section: Activated Kinases Upon Group I Mglur Stimulation With Dhpg Bmentioning

confidence: 99%

Temporal Quantitative Proteomics of mGluR-induced Protein Translation and Phosphorylation in Neurons

Gelder

Penning

Veth

et al. 2020

Molecular & Cellular Proteomics

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“…The number of Cdk5 substrates in vitro is ever growing although not all of them have been confirmed in vivo . Cdk5 directly phosphorylates many proteins involved in modulating cell morphology and motility, in neural development, and in neuronal survival or death (Dhariwala and Rajadhyaksha, 2008; Plattner et al, 2008). …”

Section: Regulation Of Cdk5mentioning

confidence: 99%

Cdk5: Mediator of neuronal development, death and the response to DNA damage

Zhu

2011

Mechanisms of Ageing and Development

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In the central nervous system, cyclin-dependent kinase 5 (Cdk5), an unusual member of the Cdk family, is implicated in the regulation of various physiological processes ranging from neuronal survival, migration and differentiation, to synaptogenesis, synaptic plasticity and neurotransmission. Dysregulation of this kinase has been demonstrated to play a critical role in the pathogenic process of neurodegenerative disorders. DNA damage is emerging as an important pathological component in various neurodegenerative conditions. In this review, we discuss the recent progress regarding the regulation and roles of Cdk5 under physiological conditions, and its dysregultion under pathological conditions, especially in neuronal death mediated by DNA damage.

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“…The interpretation of the role of Cdk5 in synaptic plasticity and spatial learning is complicated by studies revealing that transgenic mice transiently expressing p25, which is the cleaved product of p35, also show enhanced LTP and spatial learning [14][15][16]. One proposed explanation is that p25 might enhance synaptic plasticity and learning by disrupting the interaction between Cdk5 and p35, which in turn reduces degradation of the NR2B subunit of NMDA receptor [8].…”

Section: Accepted M Manuscriptmentioning

confidence: 99%

“…Second, many synaptic proteins isolated from the synaptosomes of adult brains are putative substrates of Cdk5 [7]. Finally and most importantly, the induction of synaptic plasticity, as well as hippocampus-dependent spatial learning, is affected in Cdk5 and p35 transgenic and knockout mice [8].…”

Section: Introductionmentioning

confidence: 99%

Recent advances in understanding the roles of Cdk5 in synaptic plasticity

Lai¹,

Ip²

2009

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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The molecular composition of the postsynaptic density is modified during synaptic plasticity, which forms the molecular basis of learning and memory. Such changes in synaptic composition depends in part on the intricate regulation of phosphorylation of specific proteins via different protein kinases, including a serine/threonine kinase, cyclin-dependent kinase 5 (Cdk5). However, the mechanisms underlying the involvement of Cdk5 in neural plasticity remain elusive. Recently, the identification of a number of synaptic proteins as substrates or interacting proteins with Cdk5 provides important clues on how this kinase modulates the efficacy of synaptic transmission. In this review, we summarize the recent findings to illustrate the multi-faceted roles of Cdk5 in synaptic plasticity through affecting dendritic spine formation, ion channel conductance, protein expression, and transcription in the postsynaptic neurons. Importantly, dysregulation of Cdk5 has been linked to Alzheimer's disease, which involves perturbations in synaptic functions and memory formation. Understanding the mechanisms by which Cdk5 regulates synaptic plasticity may therefore provide important insights in the design of novel therapeutic strategies for neurodegenerative diseases.

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Involvement of Cdk5 in Synaptic Plasticity, and Learning and Memory

Cited by 4 publications

References 129 publications

Temporal Quantitative Proteomics of mGluR-induced Protein Translation and Phosphorylation in Neurons

Temporal Quantitative Proteomics of mGluR-induced Protein Translation and Phosphorylation in Neurons

Cdk5: Mediator of neuronal development, death and the response to DNA damage

Recent advances in understanding the roles of Cdk5 in synaptic plasticity

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