Novel phospho-switch function of delta-catenin in dendrite development

Baumert, Ryan; Ji, Hong; Paulucci-Holthauzen, Adriana; Wolfe, Aaron; Sagum, Cari A.; Hodgson, Louis; Arikkath, Jyothi; Liu, Chen; Bedford, Mark T.; Waxham, M. Neal; McCrea, Pierre D.

doi:10.1083/jcb.201909166

Cited by 23 publications

(85 citation statements)

References 92 publications

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“…Ultimately, nascent branches are either stabilized or retracted and eliminated. Distinct molecular mechanisms underlie different aspects of dendrite growth (Vaillant et al, 2002;Baumert et al, 2020;Wilson et al, 2020). For example, glutamate-mediated signaling through mGluR5 receptors leads to Ckd5-mediated phosphorylation of delta-catenin.…”

Section: Introductionmentioning

confidence: 99%

“…For example, glutamate-mediated signaling through mGluR5 receptors leads to Ckd5-mediated phosphorylation of delta-catenin. Interestingly, unphosphorylated delta-catenin promotes extension, whereas phosphorylated delta-catenin favors branching over extension (Baumert et al, 2020). As a result, altering glutamate signaling can shift growth from extension to branching.…”

Section: Introductionmentioning

confidence: 99%

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An Autism-Associated de novo Mutation in GluN2B Destabilizes Growing Dendrites by Promoting Retraction and Pruning

Bahry

Fedder-Semmes

Sceniak

et al. 2021

Front. Cell. Neurosci.

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Mutations in GRIN2B, which encodes the GluN2B subunit of NMDA receptors, lead to autism spectrum disorders (ASD), but the pathophysiological mechanisms remain unclear. Recently, we showed that a GluN2B variant that is associated with severe ASD (GluN2B724t) impairs dendrite morphogenesis. To determine which aspects of dendrite growth are affected by GluN2B724t, we investigated the dynamics of dendrite growth and branching in rat neocortical neurons using time-lapse imaging. GluN2B724t expression shifted branch motility toward retraction and away from extension. GluN2B724t and wild-type neurons formed new branches at similar rates, but mutant neurons exhibited increased pruning of dendritic branches. The observed changes in dynamics resulted in nearly complete elimination of the net expansion of arbor size and complexity that is normally observed during this developmental period. These data demonstrate that ASD-associated mutant GluN2B interferes with dendrite morphogenesis by reducing rates of outgrowth while promoting retraction and subsequent pruning. Because mutant dendrites remain motile and capable of growth, it is possible that reducing pruning or promoting dendrite stabilization could overcome dendrite arbor defects associated with GRIN2B mutations.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

An Autism-Associated de novo Mutation in GluN2B Destabilizes Growing Dendrites by Promoting Retraction and Pruning

Bahry

Fedder-Semmes

Sceniak

et al. 2021

Front. Cell. Neurosci.

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“…Therefore, we examined whether endogenous MCHR1-positive cilia shortening is associated with the Accepted Article upregulation of PDLIM5 expression in dissociated rat hippocampal neurons. PDLIM5 is localized in the dendrites of cultured hippocampal neurons (75,76). However, in our immunohistochemical method, we could not detect PDLIM5-specific signals in soma and neurite in primary cultures of 18 DIV using an anti-PDLIM5 antibody with knockout-mediated validation (Supplemental Fig.…”

Section: Accepted Articlementioning

confidence: 88%

Ciliary GPCR‐based transcriptome as a key regulator of cilia length control

et al. 2021

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The primary cilium is a plasma membrane-protruding sensory organelle that efficiently conveys signaling cascades in a highly ordered microenvironment. Its signaling is mediated, in part, by a limited set of GPCRs preferentially enriched in the cilium membrane. This includes melanin-concentrating hormone (MCH) receptor 1 (MCHR1), which plays a role in feeding and mood. In addition to its receptor composition, the length of the cilium is a characteristic parameter that is implicated in its function. We previously found that MCH can dynamically shorten cilia length via the Gi/o and Akt pathways in both MCHR1-expressing hTERT-RPE1 cells (hRPE1 cells) and rat hippocampal neurons. However, the detailed mechanisms by which MCH regulates cilia length through ciliary MCHR1 remains unclear. In this study, we aimed to determine the transcriptome changes in MCHR1-expressing hRPE1 cells in response to MCH to identify the target molecules involved in cilia length regulation via MCHR1 activation. RNA-sequencing analysis of ciliated cells subjected to MCH treatment showed upregulation of 424 genes and downregulation of 112 genes compared with static control cells. Validation by quantitative real-time PCR, knocking down, and CRISPR/Cas9-mediated knockout technology identified a molecule, PDZ and LIM domain-containing protein 5 (PDLIM5). Thus, it was considered as the most significant key factor for MCHR1-mediated shortening of cilia length. Additional analyses revealed that the actin-binding protein alpha-actinin 1/4 is a crucial downstream target of the PDLIM5 signaling pathway that exerts an effect on MCHR1-induced cilia shortening. In the endogenous MCHR1-expressing hippocampus, transcriptional upregulation of PDLIM5 and actinin 1/4, following the application of MCH, was detected when the MCHR1-positive cilia were shortened. Together, our transcriptome study based on ciliary MCHR1 function uncovered a novel and important regulatory step underlying cilia length control. These results will potentially serve as a basis for understanding the mechanism underlying the development of obesity and mood disorders.

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“…The PDZ domain are crucial in the formation and stability of protein complexes, establishing as important bridge between extracellular stimuli and intracellular responses [49]. It has been shown that the PDZ domain of PDLIM5 interacts with α-actinin in cardiomyocytes [30]. PDLIM5 also acts as a direct binding partner for Anion exchanger 1 (AE1) via its PDZ domain for membrane targeting [50].…”

Section: Discussionmentioning

confidence: 99%

“…It has also been found that PDLIM5-PKCε interaction in the growth cone is essential for regulation of the neuronal growth cone morphology [29]. Moreover, PDLIM5 can interact with delta-catenin to form complex, which enhances dendrite branching at the expense of elongation during neuron development [30].…”

Section: Introductionmentioning

confidence: 99%

A Novel Effect of PDLIM5 In α7 Nicotinic Acetylcholine Receptors Up-Regulation And Surface Expression

Li¹,

Gou²,

Wang³

et al. 2021

Preprint

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α7 neuronal nicotinic acetylcholine receptors (α7nAChRs) are expressed widely in the brain, where they contribute to a variety of behaviors including arousal and cognition, participate in a number of neurodegenerative disorders including Alzheimer’s and Parkinson’s disease, and is responsible for nicotine addiction. Although recent studies indicate that the PDZ-containing proteins comprising PSD-95 family co-localize with nicotinic acetylcholine receptors and mediate downstream signaling in the neurons, the mechanisms by which α7nAChRs are regulated are still less well understood. Here we show that the regulation of the α7nAChRs is controlled by PDLIM5 in the endogenous PDZ domain proteins family. We find that chronic exposure to 1 μM nicotine up-regulated both α7, β2-contained nAChRs and PDLIM5 in primary cultured hippocampal neurons, and the up-regulation of α7nAChRs and PDLIM5 is increased more on the cell membrane than the cytoplasm. Interestingly, the α7nAChRs and β2nAChRs display distinct patterns of expression, with α7 co-localized more with PDLIM5. Meanwhile, PDLIM5 interacts with native brain α7 but not β2 nAChRs in neurons. Moreover, knocking down of PDLIM5 in heterologous cells abolishes nicotine-induced up-regulation of α7nAChRs. In cultured hippocampal neurons, shRNA against PDLIM5 decreased both surface clustering of α7nAChRs and α7nAChRs mediated currents. Proteomics analysis shows PDLIM5 interacts with α7nAChRs through the PDZ domain and the interaction between PDLIM5 and α7nAChRs can be promoted by nicotine. Collectively, our data suggest a novel cellular role of PDLIM5 in regulating α7nAChRs, which may be relevant to plastic changes in the nervous system.

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Novel phospho-switch function of delta-catenin in dendrite development

Cited by 23 publications

References 92 publications

An Autism-Associated de novo Mutation in GluN2B Destabilizes Growing Dendrites by Promoting Retraction and Pruning

An Autism-Associated de novo Mutation in GluN2B Destabilizes Growing Dendrites by Promoting Retraction and Pruning

Ciliary GPCR‐based transcriptome as a key regulator of cilia length control

A Novel Effect of PDLIM5 In α7 Nicotinic Acetylcholine Receptors Up-Regulation And Surface Expression

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