Pin1 Binding to Phosphorylated PSD-95 Regulates the Number of Functional Excitatory Synapses

Delgado, Jary Y.; Nall, Duncan; Selvin, Paul R

doi:10.3389/fnmol.2020.00010

Cited by 11 publications

(5 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This mechanism may explain a loss of synaptic surface PSD-95 and AMPAR during chemically induced LTD in cultured rat neurons [ 279 ]. A recent study showed that phosphorylation-dependent peptidyl-prolyl cis – trans isomerase (Pin1) binding to phosphorylated PSD-95 results in decreased palmitoylation of PSD-95, which subsequently led to a loss in the number of dendritic PSD-95 clusters, increased AMPAR mobility and a decreased number of functional excitatory synapses [ 280 ]. This data may shed light on the intertwined function of phosphorylation and palmitoylation of PSD-95 in the regulation of synaptic plasticity.…”

Section: Palmitoylation Of Ampar and Its Associated Scaffold Proteinsmentioning

confidence: 99%

Roles of palmitoylation in structural long-term synaptic plasticity

Skup

2021

Mol Brain

View full text Add to dashboard Cite

Long-term potentiation (LTP) and long-term depression (LTD) are important cellular mechanisms underlying learning and memory processes. N-Methyl-d-aspartate receptor (NMDAR)-dependent LTP and LTD play especially crucial roles in these functions, and their expression depends on changes in the number and single channel conductance of the major ionotropic glutamate receptor α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) located on the postsynaptic membrane. Structural changes in dendritic spines comprise the morphological platform and support for molecular changes in the execution of synaptic plasticity and memory storage. At the molecular level, spine morphology is directly determined by actin cytoskeleton organization within the spine and indirectly stabilized and consolidated by scaffold proteins at the spine head. Palmitoylation, as a uniquely reversible lipid modification with the ability to regulate protein membrane localization and trafficking, plays significant roles in the structural and functional regulation of LTP and LTD. Altered structural plasticity of dendritic spines is also considered a hallmark of neurodevelopmental disorders, while genetic evidence strongly links abnormal brain function to impaired palmitoylation. Numerous studies have indicated that palmitoylation contributes to morphological spine modifications. In this review, we have gathered data showing that the regulatory proteins that modulate the actin network and scaffold proteins related to AMPAR-mediated neurotransmission also undergo palmitoylation and play roles in modifying spine architecture during structural plasticity.

show abstract

Section: Palmitoylation Of Ampar and Its Associated Scaffold Proteinsmentioning

confidence: 99%

Roles of palmitoylation in structural long-term synaptic plasticity

Skup

2021

Mol Brain

View full text Add to dashboard Cite

show abstract

“…Changes in hippocampal synaptic plasticity caused by androgen deficiency include abnormal expression of synapse-associated proteins ( Zhao et al, 2018 ), decreased dendritic spine density ( Leranth et al, 2003 ), and decreased synaptic transmission efficiency ( Cooke and Woolley, 2009 ). PSD95, a scaffold protein, is primarily located in the excitatory glutamic energy postsynaptic membrane ( Delgado et al, 2020 ). PSD95 is a key protein that promotes synapse maturation and maintains the stability of dendritic spines ( Ampuero et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

CaMKII is a modulator in neurodegenerative diseases and mediates the effect of androgen on synaptic protein PSD95

Chen

Lin

et al. 2022

Front. Genet.

View full text Add to dashboard Cite

Androgens rapidly regulate synaptic plasticity in hippocampal neurones, but the underlying mechanisms remain unclear. In this study, we carried out a comprehensive bioinformatics analysis of functional similarities between androgen receptor (AR) and the synaptic protein postsynaptic density 95 (PSD95) to evaluate the effect. Using different measurements and thresholds, we obtained consistent results illustrating that the two proteins were significantly involved in similar pathways. We further identified CaMKII plays a critical role in mediating the rapid effect of androgen and promoting the expression of PSD95. We used mouse hippocampal neurone HT22 cells as a cell model to investigate the effect of testosterone (T) on intracellular Ca2+ levels and the mechanism. Calcium imaging experiments showed that intracellular Ca2+ increased to a peak due to calcium influx in the extracellular fluid through L-type and N-type voltage-gated calcium channels when HT22 cells were treated with 100 nM T for 20 min. Subsequently, we investigated whether the Ca2+/CaMKII signaling pathway mediates the rapid effect of T, promoting the expression of the synaptic protein PSD95. Immunofluorescence cytochemical staining and western blotting results showed that T promoted CaMKII phosphorylation by rapidly increasing extracellular Ca2+ influx, thus increasing PSD95 expression. This study demonstrated that CaMKII acts as a mediator assisting androgen which regulates the synaptic protein PSD95Also, it provides evidence for the neuroprotective mechanisms of androgens in synaptic plasticity and reveals the gated and pharmacological mechanisms of the voltage-gated Ca2+ channel family for androgen replacement therapy.

show abstract

“…180 PSD-95: Postsynaptic density protein-95 (PSD-95) is a membrane-associated scaffold protein that plays a central role in the development of synapse development, number, stabilization, and function. [192][193][194] A well-studied action of PSD-95 is the anchoring AMPA and NMDA receptors in the postsynaptic terminal, which regulates neurotransmission by glutamate. 195 Not surprisingly, altered PSD-95 function has been implicated in epilepsy.…”

Section: Potential Common Effectorsmentioning

confidence: 99%

Rett and Rett-related disorders: Common mechanisms for shared symptoms?

D’Mello

2023

Exp Biol Med (Maywood)

View full text Add to dashboard Cite

Rett syndrome is a neurodevelopmental disorder caused by loss-of-function mutations in the methyl-CpG binding protein-2 (MeCP2) gene that is characterized by epilepsy, intellectual disability, autistic features, speech deficits, and sleep and breathing abnormalities. Neurologically, patients with all three disorders display microcephaly, aberrant dendritic morphology, reduced spine density, and an imbalance of excitatory/inhibitory signaling. Loss-of-function mutations in the cyclin-dependent kinase-like 5 (CDKL5) and FOXG1 genes also cause similar behavioral and neurobiological defects and were referred to as congenital or variant Rett syndrome. The relatively recent realization that CDKL5 deficiency disorder (CDD), FOXG1 syndrome, and Rett syndrome are distinct neurodevelopmental disorders with some distinctive features have resulted in separate focus being placed on each disorder with the assumption that distinct molecular mechanisms underlie their pathogenesis. However, given that many of the core symptoms and neurological features are shared, it is likely that the disorders share some critical molecular underpinnings. This review discusses the possibility that deregulation of common molecules in neurons and astrocytes plays a central role in key behavioral and neurological abnormalities in all three disorders. These include KCC2, a chloride transporter, vGlut1, a vesicular glutamate transporter, GluD1, an orphan-glutamate receptor subunit, and PSD-95, a postsynaptic scaffolding protein. We propose that reduced expression or activity of KCC2, vGlut1, PSD-95, and AKT, along with increased expression of GluD1, is involved in the excitatory/inhibitory that represents a key aspect in all three disorders. In addition, astrocyte-derived brain-derived neurotrophic factor (BDNF), insulin-like growth factor 1 (IGF-1), and inflammatory cytokines likely affect the expression and functioning of these molecules resulting in disease-associated abnormalities.

show abstract

Pin1 Binding to Phosphorylated PSD-95 Regulates the Number of Functional Excitatory Synapses

Cited by 11 publications

References 53 publications

Roles of palmitoylation in structural long-term synaptic plasticity

Roles of palmitoylation in structural long-term synaptic plasticity

CaMKII is a modulator in neurodegenerative diseases and mediates the effect of androgen on synaptic protein PSD95

Rett and Rett-related disorders: Common mechanisms for shared symptoms?

Contact Info

Product

Resources

About