Actinin-4 Governs Dendritic Spine Dynamics and Promotes Their Remodeling by Metabotropic Glutamate Receptors

Kalinowska, Magdalena; Chávez, Andrés E.; Lutzu, Stefano; Castillo, Pablo E.; Bukauskas, Feliksas F.; Francesconi, Anna

doi:10.1074/jbc.m115.640136

Cited by 42 publications

(42 citation statements)

References 80 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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

View full text Add to dashboard Cite

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.

show abstract

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

View full text Add to dashboard Cite

show abstract

“…α-actinin selectively stabilizes CaMKII association with GluN2B-containing glutamate receptors [104]. The isoform α-actinin-4 is an interacting partner of metabotropic glutamate receptors and orchestrates spine dynamics and morphogenesis in neurons through a CaMKIIβ-dependent process [105].…”

Section: Tropomyosinsmentioning

confidence: 99%

Dendritic Spines in Alzheimer’s Disease: How the Actin Cytoskeleton Contributes to Synaptic Failure

Pelucchi

Stringhi

Marcello

2020

IJMS

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by Aβ-driven synaptic dysfunction in the early phases of pathogenesis. In the synaptic context, the actin cytoskeleton is a crucial element to maintain the dendritic spine architecture and to orchestrate the spine’s morphology remodeling driven by synaptic activity. Indeed, spine shape and synaptic strength are strictly correlated and precisely governed during plasticity phenomena in order to convert short-term alterations of synaptic strength into long-lasting changes that are embedded in stable structural modification. These functional and structural modifications are considered the biological basis of learning and memory processes. In this review we discussed the existing evidence regarding the role of the spine actin cytoskeleton in AD synaptic failure. We revised the physiological function of the actin cytoskeleton in the spine shaping and the contribution of actin dynamics in the endocytosis mechanism. The internalization process is implicated in different aspects of AD since it controls both glutamate receptor membrane levels and amyloid generation. The detailed understanding of the mechanisms controlling the actin cytoskeleton in a unique biological context as the dendritic spine could pave the way to the development of innovative synapse-tailored therapeutic interventions and to the identification of novel biomarkers to monitor synaptic loss in AD.

show abstract

“…In addition to creating bundles, actin crosslinkers often protect filaments from depolymerization or at least slow down the depolymerization rate. The actin cross-linkers which have been shown to play a role in morphological dendritic spine maturation are non-muscle myosin IIb [97][98][99] , calcium calmodulin kinase II (CaMKII 100 , drebrin [101][102][103] , α-actinin-2 104 and α-actinin-4 105 . In addition to these functions, actin cross-linkers often provide a scaffolding platform for protein interaction and many of them link synaptic receptors to the actin cytoskeleton.…”

Section: Actin Cross-linking Proteinsmentioning

confidence: 99%

“…All isoforms, except α-actinin-3, are found in the brain 108 , with α-actinin-4 being expressed in the hippocampus, cortex, and cerebellum 105 . The full-length human α-actinin-4 protein is divided into three functional subdomains: The N-terminal actin-binding domain,…”

Section: Actin Cross-linking Proteinsmentioning

confidence: 99%

Dendritic spine actin cytoskeleton in autism spectrum disorder

Joensuu¹,

Lanoue

Hotulainen

2018

Progress in Neuro-Psychopharmacology and Biological Psychiatry

View full text Add to dashboard Cite

Actinin-4 Governs Dendritic Spine Dynamics and Promotes Their Remodeling by Metabotropic Glutamate Receptors

Cited by 42 publications

References 80 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

Dendritic Spines in Alzheimer’s Disease: How the Actin Cytoskeleton Contributes to Synaptic Failure

Dendritic spine actin cytoskeleton in autism spectrum disorder

Contact Info

Product

Resources

About