Peroxiredoxin 5 Decreases Beta-Amyloid-Mediated Cyclin-Dependent Kinase 5 Activation Through Regulation of Ca<sup>2+</sup>-Mediated Calpain Activation

Park, Junghyung; Chae, Unbin; Lee, Dong Seok; Kam, Min Kyoung; Lee, Sang-Rae; Lee, Seung‐Hoon; Lee, Hyun‐Shik; Park, Jeen‐Woo

doi:10.1089/ars.2016.6810

Cited by 25 publications

(32 citation statements)

References 58 publications

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“…We have detected differentially interacting proteins by comparing data sets from the hippocampus and the CA3 subfield of the hippocampus. All the CA3 (PSD95-cTAP; Grik4 Cre) enriched proteins (Abr, Actn4, Bai3, Cacng8, Grik2, Hist1h2al, Mbp, Nlgn3 and Prdx5) have been reported to have important functions in brain that include roles in synapse formation, synaptic plasticity and psychiatric disorders (Duman, Tu, & Tolias, 2016;Ge et al, 2016;Kalinowska et al, 2015;Lanoue et al, 2013;Malty et al, 2017;Martinelli et al, 2016;Oh et al, 2010;Park et al, 2017;Sigoillot et al, 2015;Walikonis et al, 2001;Yamagata et al, 2017). This might indicate that different types of PSD95 complexes exist in different brain regions with distinct functions.…”

Section: Discussionmentioning

confidence: 99%

Cell‐type‐specific visualisation and biochemical isolation of endogenous synaptic proteins in mice

Zhu

Collins

Harmse

et al. 2019

Eur J of Neuroscience

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In recent years, the remarkable molecular complexity of synapses has been revealed, with over 1,000 proteins identified in the synapse proteome. Although it is known that different receptors and other synaptic proteins are present in different types of neurons, the extent of synapse diversity across the brain is largely unknown. This is mainly due to the limitations of current techniques. Here, we report an efficient method for the purification of synaptic protein complexes, fusing a high‐affinity tag to endogenous PSD95 in specific cell types. We also developed a strategy, which enables the visualisation of endogenous PSD95 with fluorescent‐protein tag in Cre‐recombinase‐expressing cells. We demonstrate the feasibility of proteomic analysis of synaptic protein complexes and visualisation of these in specific cell types. We find that the composition of PSD95 complexes purified from specific cell types differs from those extracted from tissues with diverse cellular composition. The results suggest that there might be differential interactions in the PSD95 complexes in different brain regions. We have detected differentially interacting proteins by comparing data sets from the whole hippocampus and the CA3 subfield of the hippocampus. Therefore, these novel conditional PSD95 tagging lines will not only serve as powerful tools for precisely dissecting synapse diversity in specific brain regions and subsets of neuronal cells, but also provide an opportunity to better understand brain region‐ and cell‐type‐specific alterations associated with various psychiatric/neurological diseases. These newly developed conditional gene tagging methods can be applied to many different synaptic proteins and will facilitate research on the molecular complexity of synapses.

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Section: Discussionmentioning

confidence: 99%

Cell‐type‐specific visualisation and biochemical isolation of endogenous synaptic proteins in mice

Zhu

Collins

Harmse

et al. 2019

Eur J of Neuroscience

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“…Previous studies have demonstrated that regulation of CDK5 is essential for early neuronal development and differentiation. CDK5 activation, by conversion of p35 to p25, is triggered by calpain activation, which is mediated by intracellular Ca 2+ levels [40]. Here, we studied the effect of CDK5-regulated Wnt signaling.…”

Section: Discussionmentioning

confidence: 99%

Wnt-5a Promotes Neural Development and Differentiation by Regulating CDK5 via Ca2+/Calpain Pathway

Yang

Xiang

Zhang

et al. 2018

Cell Physiol Biochem

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Background/Aims: The Wnt signaling pathway has essential functions in the central nervous system, where it regulates the major physiological functions of neurons, including development, differentiation, and plasticity. Wnt signaling controls these cellular events; however, how Wnt pathways integrate into a coherent developmental program remains unclear. Methods: The expression and secretion of different WNT ligands (Wnt-1, Wnt-3a, Wnt-4, Wnt-5a, Wnt-11), and the levels and activities of cyclin-dependent kinases (CDK2, CDK4, CDK6/cyclin D, cyclin E) or CDK5 (CDK5/p35 and p25) were measured in Rat cortex at different embryonic stages, and in RA/BDNF-induced differentiated SH-SY5Y cell model, by Quantitative real-time PCR (qPCR), western blotting, ELISA, and in vitro CDK5 kinase assays. MAP2-BrdU double staining was used to assess cell differentiation and cell cycle exit in an RA/BDNF-induced differentiated SH-SY5Y cell model. The effects of CDK5 and Ca²⁺/calpain signaling were assessed using specific chemical inhibitors. Results: We found that Wnt-1 was unchanged and Wnt-3a was attenuated, whereas Wnt-4, Wnt-5a, and Wnt-11 were markedly up-regulated, during the development of neurons and differentiated SH-SY5Y cells. Simultaneously, the activity of CDK5 was elevated. Furthermore, we describe crosstalk between non-canonical Wnt signaling and CDK5 in the development of neurons and differentiated SH-SY5Y cells. Wnt-5a, a non-canonical Wnt ligand, regulated CDK5 via Ca²⁺/calpain signaling in both neuronal development and differentiation. Inhibition of Wnt-5a diminished CDK5 kinase activity via the Ca²⁺/calpain pathway, thereby attenuating RA-BDNF induced SH-SY5Y cell differentiation. Conclusion: Wnt-5a signaling is a significant regulator of neuronal development and differentiation and upregulates CDK5 kinase activity via Ca²⁺/calpain signaling.

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“…have been reported to have important functions in brain that include roles for synapse formation, synaptic plasticity and psychiatric disorder (Walikonis et al, 2001;Oh et al, 2010;Lanoue et al, 2013;Kalinowska et al, 2015;Sigoillot et al, 2015;Duman et al, 2016;Ge et al, 2016;Martinelli et al, 2016;Malty et al, 2017;Park et al, 2017;Yamagata et al, 2017). This might implicate that different types of PSD95 complexes exist in different brain regions with distinct functions.…”

Section: Discussionmentioning

confidence: 99%

Cell-type specific visualization and biochemical isolation of endogenous synaptic proteins in mice

Zhu

Collins

Harmse

et al. 2018

Preprint

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In recent years, the remarkable molecular complexity of synapses has been revealed, with over 1000 proteins identified in the synapse proteome. Although it is known that different receptors and other synaptic proteins are present in different types of neurons and synapses, the extent of synapse diversity across the brain is largely unknown, mainly owing to technical limitations. Combining mouse genetics and proteomics we have previously reported highly efficient methods for purification of synaptic protein complexes under native conditions. In that approach, tandem affinity purification (TAP) tags were fused to the carboxyl terminus of PSD95 using gene targeting in mice. Here we report an approach that restricts tagging of endogenous PSD95 to cells expressing Cre recombinase. In addition, we developed a labelling strategy enabling visualization of endogenous PSD95 tagged by fluorescent proteins in Cre-expressing cells. We demonstrate the feasibility of proteomic characterisation of synapse proteomes and visualization of synapse proteins in specific cell types. We find that composition of PSD95 complexes purified from specific cell types differs from those extracted from tissues with diverse cellular composition. Therefore, these novel conditional PSD95 tagging lines will not only serve as powerful tools for precisely dissecting synapse diversity in specific subsets of regions/neuronal cells, but also provide an opportunity to better understand brain region-specific alterations associated with various psychiatric/neurological diseases. The newly developed conditional gene tagging methods can be applied to many different synaptic proteins and will thus facilitate research on the molecular complexity of synapses.

show abstract

Peroxiredoxin 5 Decreases Beta-Amyloid-Mediated Cyclin-Dependent Kinase 5 Activation Through Regulation of Ca²⁺-Mediated Calpain Activation

Cited by 25 publications

References 58 publications

Cell‐type‐specific visualisation and biochemical isolation of endogenous synaptic proteins in mice

Cell‐type‐specific visualisation and biochemical isolation of endogenous synaptic proteins in mice

Wnt-5a Promotes Neural Development and Differentiation by Regulating CDK5 via Ca2+/Calpain Pathway

Cell-type specific visualization and biochemical isolation of endogenous synaptic proteins in mice

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Peroxiredoxin 5 Decreases Beta-Amyloid-Mediated Cyclin-Dependent Kinase 5 Activation Through Regulation of Ca2+-Mediated Calpain Activation

Cited by 25 publications

References 58 publications

Cell‐type‐specific visualisation and biochemical isolation of endogenous synaptic proteins in mice

Cell‐type‐specific visualisation and biochemical isolation of endogenous synaptic proteins in mice

Wnt-5a Promotes Neural Development and Differentiation by Regulating CDK5 via Ca2+/Calpain Pathway

Cell-type specific visualization and biochemical isolation of endogenous synaptic proteins in mice

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Peroxiredoxin 5 Decreases Beta-Amyloid-Mediated Cyclin-Dependent Kinase 5 Activation Through Regulation of Ca²⁺-Mediated Calpain Activation