Cellular prion protein: A co-receptor mediating neuronal cofilin-actin rod formation induced by β-amyloid and proinflammatory cytokines

Walsh, Keifer P.; Kühn, Thomas; Bamburg, James R.

doi:10.4161/pri.35504

Cited by 19 publications

(18 citation statements)

References 40 publications

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“…Our findings are in agreement with previously reported data showing increased cytoskeletal stability, RhoA activation and cofilin inactivation in PrP-deficient neuronal cells (Loubet et al, 2012). Interestingly, overexpression of PrP in primary rat hippocampal neurons induces cofilin activation and the formation of actin-cofilin rods (Walsh et al, 2014). These structures are found in Alzheimer disease brain and have been shown to impair synaptic function (Minamide et al, 2000).…”

Section: Discussionsupporting

confidence: 93%

The prion protein inhibits monocytic cell migration by stimulating β1 integrin adhesion and uropod formation

Richardson

Tol

Valle-Encinas

et al. 2015

Journal of Cell Science

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The broad tissue distribution and evolutionary conservation of the glycosylphosphatidylinositol (GPI)-anchored prion protein (PrP, also known as PRNP) suggests that it plays a role in cellular homeostasis. Given that integrin adhesion determines cell behavior, the proposed role of PrP in cell adhesion might underlie the various in vitro and in vivo effects associated with PrP loss-of-function, including the immune phenotypes described in PrP −/− mice. Here, we investigated the role of PrP in the adhesion and (transendothelial) migration of human ( pro)monocytes. We found that PrP regulates β1-integrinmediated adhesion of monocytes. Additionally, PrP controls the cell morphology and migratory behavior of monocytes: PrP-silenced cells show deficient uropod formation on immobilized VCAM and display bleb-like protrusions on the endothelium. Our data further show that PrP regulates ligand-induced integrin activation. Finally, we found that PrP controls the activation of several proteins involved in cell adhesion and migration, including RhoA and its effector cofilin, as well as proteins of the ERM family. We propose that PrP modulates β1 integrin adhesion and migration of monocytes through RhoA-induced actin remodeling mediated by cofilin, and through the regulation of ERM-mediated membrane-cytoskeleton linkage.

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Section: Discussionsupporting

confidence: 93%

The prion protein inhibits monocytic cell migration by stimulating β1 integrin adhesion and uropod formation

Richardson

Tol

Valle-Encinas

et al. 2015

Journal of Cell Science

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“…Specifically, a study by Rahman and colleagues reported a 4-fold increase in cofilin rods/aggregates in AD versus age-matched controls, which correlates with the extent of tauopathy [85]. Previous studies have also shown that bioactive A␤ dimers/trimers at subnanomolar concentrations promote cofilin-actin rod formation in a subset of neurons associated with activation of cofilin and NADPH oxidase (NOX) [33,70,82,86]. While it is not clear whether cofilin-actin pathology plays an essential role in AD pathogenesis, it is certainly a pathology saliently present in AD brains Intramolecular disulfide bridging of oxidized and activated cofilin loses affinity for actin and translocates to mitochondria to promotes mitochondrial dysfunction together with p53 and Drp1.…”

Section: Cofilin-actin Pathologymentioning

confidence: 99%

Cofilin, a Master Node Regulating Cytoskeletal Pathogenesis in Alzheimer’s Disease

Kang

Woo

2019

JAD

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The defining pathological hallmarks of Alzheimer's disease (AD) are proteinopathies marked by the amyloid-␤ (A␤) peptide and hyperphosphorylated tau. In addition, Hirano bodies and cofilin-actin rods are extensively found in AD brains, both of which are associated with the actin cytoskeleton. The actin-binding protein cofilin known for its actin filament severing, depolymerizing, nucleating, and bundling activities has emerged as a significant player in AD pathogenesis. In this review, we discuss the regulation of cofilin by multiple signaling events impinging on LIM kinase-1 (LIMK1) and/or Slingshot homolog-1 (SSH1) downstream of A␤. Such pathophysiological signaling pathways impact actin dynamics to regulate synaptic integrity, mitochondrial translocation of cofilin to promote neurotoxicity, and formation of cofilin-actin pathology. Other intracellular signaling proteins, such as ␤-arrestin, RanBP9, Chronophin, PLD1, and 14-3-3 also impinge on the regulation of cofilin downstream of A␤. Finally, we discuss the role of activated cofilin as a bridge between actin and microtubule dynamics by displacing tau from microtubules, thereby destabilizing tau-induced microtubule assembly, missorting tau, and promoting tauopathy.

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“…Interestingly, Amyloid bprotein precursor (AbPP) is also upregulated in the FXS mouse model (Napoli et al, 2008). b-amyloid induces the formation of cytoplasmic rod-shaped bundles of filaments composed of cofilin and actin in Alzheimer's disease (Walsh et al, 2014). Cofilin binds actin subunits in F-actin, a key element on spine morphological remodeling, and severs actin filaments at low cofilin/actin ratios while stabilizes them at high cofilin/actin ratios (Bamburg and Bernstein, 2016).…”

Section: Fragile X Mental Retardation Gene (Fmr1)mentioning

confidence: 99%

Dendrite and spine modifications in autism and related neurodevelopmental disorders in patients and animal models

Martínez‐Cerdeño

2016

Developmental Neurobiology

200

127

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Dendrites and spines are the main neuronal structures receiving input from other neurons and glial cells. Dendritic and spine number, size and morphology are some of the crucial factors determining how signals coming from individual synapses are integrated. Much remains to be understood about the characteristics of neuronal dendrites and dendritic spines in autism and related disorders. Though there have been many studies conducted using autism mouse models, few have been carried out using postmortem human tissue from patients. Available animal models of autism include those generated thought genetic modifications and those non-genetic models of the disease. Here, we review how dendrite and spine morphology and number is affected in autism and related neurodevelopmental diseases, both in human, and genetic and non-genetic animal models of autism. Overall, data obtained from human and animal models point to a generalized reduction in the size and number together with an alteration of the morphology of dendrites; and an increase in spine densities with immature morphology, indicating a general spine immaturity state in autism. Additional human studies on dendrite and spine number and morphology in postmortem tissue are needed to understand the properties of these structures in the cerebral cortex of patients with autism.

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Cellular prion protein: A co-receptor mediating neuronal cofilin-actin rod formation induced by β-amyloid and proinflammatory cytokines

Cited by 19 publications

References 40 publications

The prion protein inhibits monocytic cell migration by stimulating β1 integrin adhesion and uropod formation

The prion protein inhibits monocytic cell migration by stimulating β1 integrin adhesion and uropod formation

Cofilin, a Master Node Regulating Cytoskeletal Pathogenesis in Alzheimer’s Disease

Dendrite and spine modifications in autism and related neurodevelopmental disorders in patients and animal models

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