Rapid Changes in Phospho-MAP/Tau Epitopes during Neuronal Stress: Cofilin-Actin Rods Primarily Recruit Microtubule Binding Domain Epitopes

Whiteman, Ineka T.; Minamide, Laurie S.; Goh, De Lian; Bamburg, James R.; Goldsbury, Claire

doi:10.1371/journal.pone.0020878

Cited by 27 publications

(31 citation statements)

References 67 publications

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“…AT100 staining showed the previously described, unspecific nuclear localization [32]. Biochemical analysis did not reveal an age-dependent increase of total, insoluble or phosphorylated tau (Fig.…”

Section: Discussionsupporting

confidence: 70%

Revisiting rodent models: Octodon degus as Alzheimer’s disease model?

Steffen

Krohn

Paarmann

et al. 2016

acta neuropathol commun

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Alzheimer’s disease primarily occurs as sporadic disease and is accompanied with vast socio-economic problems. The mandatory basic research relies on robust and reliable disease models to overcome increasing incidence and emerging social challenges. Rodent models are most efficient, versatile, and predominantly used in research. However, only highly artificial and mostly genetically modified models are available. As these ‘engineered’ models reproduce only isolated features, researchers demand more suitable models of sporadic neurodegenerative diseases. One very promising animal model was the South American rodent Octodon degus, which was repeatedly described as natural ‘sporadic Alzheimer’s disease model’ with ‘Alzheimer’s disease-like neuropathology’. To unveil advantages over the ‘artificial’ mouse models, we re-evaluated the age-dependent, neurohistological changes in young and aged Octodon degus (1 to 5-years-old) bred in a wild-type colony in Germany. In our hands, extensive neuropathological analyses of young and aged animals revealed normal age-related cortical changes without obvious signs for extensive degeneration as seen in patients with dementia. Neither significant neuronal loss nor enhanced microglial activation were observed in aged animals. Silver impregnation methods, conventional, and immunohistological stains as well as biochemical fractionations revealed neither amyloid accumulation nor tangle formation. Phosphoepitope-specific antibodies against tau species displayed similar intraneuronal reactivity in both, young and aged Octodon degus.In contrast to previous results, our study suggests that Octodon degus born and bred in captivity do not inevitably develop cortical amyloidosis, tangle formation or neuronal loss as seen in Alzheimer’s disease patients or transgenic disease models.

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Section: Discussionsupporting

confidence: 70%

Revisiting rodent models: Octodon degus as Alzheimer’s disease model?

Steffen

Krohn

Paarmann

et al. 2016

acta neuropathol commun

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“…32 Studies using mice later demonstrated that cofilin rods might influence microtubule organization and intracellular trafficking by affecting the redistribution and phosphorylation of microtubule associated protein. 33,34 Together, these studies strongly support the hypothesis that cofilin may be involved in the regulation of tubulin dynamics and stability, and thereby platelet production in MKs.…”

Section: Discussionsupporting

confidence: 67%

Defective tubulin organization and proplatelet formation in murine megakaryocytes lacking Rac1 and Cdc42

Pleines

Dütting

Cherpokova

et al. 2013

Blood

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Key Points• Rac1 and Cdc42 have redundant functions in platelet biogenesis. • Deficiency of Rac1 andCdc42 results in highly abnormal megakaryocyte morphology associated with severely defective tubulin organization.Blood platelets are anuclear cell fragments that are essential for blood clotting. Platelets are produced by bone marrow megakaryocytes (MKs), which extend protrusions, or socalled proplatelets, into bone marrow sinusoids. Proplatelet formation requires a profound reorganization of the MK actin and tubulin cytoskeleton. Rho GTPases, such as RhoA, Rac1, and Cdc42, are important regulators of cytoskeletal rearrangements in platelets; however, the specific roles of these proteins during platelet production have not been established. Using conditional knockout mice, we show here that Rac1 and Cdc42 possess redundant functions in platelet production and function. In contrast to a singledeficiency of either protein, a double-deficiency of Rac1 and Cdc42 in MKs resulted in macrothrombocytopenia, abnormal platelet morphology, and impaired platelet function. Double-deficient bone marrow MKs matured normally in vivo but displayed highly abnormal morphology and uncontrolled fragmentation. Consistently, a lack of Rac1/ Cdc42 virtually abrogated proplatelet formation in vitro. Strikingly, this phenotype was associated with severely defective tubulin organization, whereas actin assembly and structure were barely affected. Together, these results suggest that the combined action of Rac1 and Cdc42 is crucial for platelet production, particularly by regulating microtubule dynamics. (Blood. 2013;122(18):3178-3187)

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“…3; [8]), and the loss of neuronal integrity may be affecting total and phosphorylated tau levels in the neuron. A recent study [29] demonstrated that after antimycin A treatment, the presence of Ser 262/356 ‐tau increases, while total tau and tau phosphorylated at Ser 396/404 decreases. This was shown to be a result of the specific recruitment of Ser 262/356 ‐tau to actin‐cofilin rods.…”

Section: Discussionmentioning

confidence: 98%

Decreases in valosin-containing protein result in increased levels of tau phosphorylated at Ser^262/356

et al. 2011

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VCP/p97 is a multifunctional AAA+-ATPase involved in vesicle fusion, proteasomal degradation, and autophagy. Reported dysfunctions of these processes in Alzheimer disease (AD), along with the linkage of VCP/p97 to inclusion body myopathy with Paget’s disease and frontotemporal dementia (IBMPFD) led us to examine the possible linkage of VCP to the AD-relevant protein, tau. VCP levels were reduced in AD brains, but not in the cerebral cortex of an AD mouse model, suggesting that VCP reduction occurs upstream of tau pathology. Genetic reduction of VCP in a primary neuronal model led to increases in the levels of tau phosphorylated at Ser262/356, indicating that VCP may be involved in regulating post-translational processing of tau in AD, demonstrating a possible functional linkage between tau and VCP.

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Rapid Changes in Phospho-MAP/Tau Epitopes during Neuronal Stress: Cofilin-Actin Rods Primarily Recruit Microtubule Binding Domain Epitopes

Cited by 27 publications

References 67 publications

Revisiting rodent models: Octodon degus as Alzheimer’s disease model?

Revisiting rodent models: Octodon degus as Alzheimer’s disease model?

Defective tubulin organization and proplatelet formation in murine megakaryocytes lacking Rac1 and Cdc42

Decreases in valosin-containing protein result in increased levels of tau phosphorylated at Ser^262/356

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Rapid Changes in Phospho-MAP/Tau Epitopes during Neuronal Stress: Cofilin-Actin Rods Primarily Recruit Microtubule Binding Domain Epitopes

Cited by 27 publications

References 67 publications

Revisiting rodent models: Octodon degus as Alzheimer’s disease model?

Revisiting rodent models: Octodon degus as Alzheimer’s disease model?

Defective tubulin organization and proplatelet formation in murine megakaryocytes lacking Rac1 and Cdc42

Decreases in valosin-containing protein result in increased levels of tau phosphorylated at Ser262/356

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Product

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Decreases in valosin-containing protein result in increased levels of tau phosphorylated at Ser^262/356