Unbiased proteomic profiling reveals the IP3R modulator AHCYL1/IRBIT as a novel interactor of microtubule-associated protein tau

Wischhof, Lena; Adhikari, Aasha; Mondal, Mrityunjoy; Marsal-Cots, Anaïs; Biernat, Jacek; Mandelkow, E.; Mandelkow, Eckhard; Ehninger, Dan; Nicotera, Pierluigi; Bano, Daniele

doi:10.1016/j.jbc.2022.101774

Cited by 5 publications

(6 citation statements)

References 70 publications

(125 reference statements)

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“…Also, low expression of AHCYL1 was associated with poor prognosis and recurrence in gastric cancer [ 16 ]. A recent report indicated that AHCYL1 negatively regulates autophagy in U20S and Hela cancer cells [ 17 , 18 ]. In addition, AHCYL1 can inhibit S-Adenosylhomocysteine hydrolase (AHCY), a key enzyme that reversibly catalyzes the hydrolysis of S-Adenosylhomocysteine (SAH) to Homocysteine (Hcy) and Adenosine [ 10 , 19 ], and Ribonucleotide reductase (RNR), which is required for cell cycle progression [ 12 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

S-adenosylhomocysteine hydrolase-like protein 1 (AHCYL1) inhibits lung cancer tumorigenesis by regulating cell plasticity

et al. 2023

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Background Lung cancer is one of the most frequently diagnosed cancers characterized by high mortality, metastatic potential, and recurrence. Deregulated gene expression of lung cancer, likewise in many other solid tumors, accounts for their cell heterogeneity and plasticity. S-adenosylhomocysteine hydrolase-like protein 1 (AHCYL1), also known as Inositol triphosphate (IP(3)) receptor-binding protein released with IP(3) (IRBIT), plays roles in many cellular functions, including autophagy and apoptosis but AHCYL1 role in lung cancer is largely unknown. Results Here, we analyzed the expression of AHCYL1 in Non-Small Cell Lung Cancer (NSCLC) cells from RNA-seq public data and surgical specimens, which revealed that AHCYL1 expression is downregulated in tumors and inverse correlated to proliferation marker Ki67 and the stemness signature expression. AHCYL1-silenced NSCLC cells showed enhanced stem-like properties in vitro, which correlated with higher expression levels of stem markers POU5F1 and CD133. Also, the lack of AHCYL1 enhanced tumorigenicity and angiogenesis in mouse xenograft models highlighting stemness features. Conclusions These findings indicate that AHCYL1 is a negative regulator in NSCLC tumorigenesis by modulating cell differentiation state and highlighting AHCYL1 as a potential prognostic biomarker for lung cancer.

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Section: Introductionmentioning

confidence: 99%

S-adenosylhomocysteine hydrolase-like protein 1 (AHCYL1) inhibits lung cancer tumorigenesis by regulating cell plasticity

et al. 2023

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“…To corroborate our findings using an additional method, we employed high-content protein microchips consisting of more than 9.000 human polypeptides. Following the same approach as described in one of our prior works [ 31 ], two separate microarrays were incubated with 5 or 50 ng of monomeric α-Syn. After development with primary and fluorescently labeled secondary antibodies, we identified 158 putative polypeptides that could physically interact with α-Syn in vitro (Fig.…”

Section: Resultsmentioning

confidence: 99%

Actin-nucleation promoting factor N-WASP influences alpha-synuclein condensates and pathology

Jackson,

Hoffmann,

Scifo

et al. 2024

Cell Death Dis

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Abnormal intraneuronal accumulation of soluble and insoluble α-synuclein (α-Syn) is one of the main pathological hallmarks of synucleinopathies, such as Parkinson’s disease (PD). It has been well documented that the reversible liquid-liquid phase separation of α-Syn can modulate synaptic vesicle condensates at the presynaptic terminals. However, α-Syn can also form liquid-like droplets that may convert into amyloid-enriched hydrogels or fibrillar polymorphs under stressful conditions. To advance our understanding on the mechanisms underlying α-Syn phase transition, we employed a series of unbiased proteomic analyses and found that actin and actin regulators are part of the α-Syn interactome. We focused on Neural Wiskott-Aldrich syndrome protein (N-WASP) because of its association with a rare early-onset familial form of PD. In cultured cells, we demonstrate that N-WASP undergoes phase separation and can be recruited to synapsin 1 liquid-like droplets, whereas it is excluded from α-Syn/synapsin 1 condensates. Consistently, we provide evidence that wsp-1/WASL loss of function alters the number and dynamics of α-Syn inclusions in the nematode Caenorhabditis elegans. Together, our findings indicate that N-WASP expression may create permissive conditions that promote α-Syn condensates and their potentially deleterious conversion into toxic species.

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“…(1) Reviews, (2) case reports, (3) editorials, (4) conference papers, (5) studies on irrelevant topics, (6) studies that were not performed in vivo, (7) studies with an absence of a control group, (8) studies with no available data, and (9) studies in which Sal administration was combined with other drugs were excluded.…”

Section: Search Strategymentioning

confidence: 99%

“…Aβ 48 and Aβ 49 can continue to be cleaved by γ-secretase in a 3–4 residue manner to generate short peptide products of different lengths, and the long-term accumulation of these Aβ short peptides can lead to the formation of Aβ plaques, which cause AD symptoms, such as memory and cognitive impairment . Tau is the major microtubule-associated protein of mature neurons and regulates many physiological processes by binding directly or indirectly to molecular partners . Hyperphosphorylated tau proteins cannot bind to microtubule proteins, forming NFTs .…”

Section: Introductionmentioning

confidence: 99%

“…6 Tau is the major microtubule-associated protein of mature neurons and regulates many physiological processes by binding directly or indirectly to molecular partners. 7 Hyperphosphorylated tau proteins cannot bind to microtubule proteins, forming NFTs. 8 A recent important study found that tau proteins are also involved in activating antiviral pathways and inhibit neuronal repair, ultimately leading to tau protein-induced cognitive impairment.…”

Section: Introductionmentioning

confidence: 99%

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Neuroprotective Mechanisms of Salidroside in Alzheimer’s Disease: A Systematic Review and Meta-analysis of Preclinical Studies

Zhang,

Nao,

Dong

2023

J. Agric. Food Chem.

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Alzheimer’s disease (AD) is a neurodegenerative disease of the central nervous system that occurs in old age and pre-aging, characterized by progressive cognitive dysfunction and behavioral impairment. Salidroside (Sal) is a phenylpropanoid mainly isolated from Rhodiola species with various pharmacological effects. However, the exact anti-AD mechanism of Sal has not been clearly elucidated. This meta-analysis aims to investigate the possible mechanisms by which Sal exerts its anti-AD effects by evaluating behavioral indicators and biochemical characteristics. A total of 20 studies were included, and the results showed that the Sal treatment significantly improved behavior abnormalities in AD animal models. With regard to neurobiochemical indicators, Sal treatment could effectively increase the antioxidant enzyme superoxide dismutase, decrease the oxidative stress indicator malondialdehyde, and decrease the inflammatory indicators interleukin 1β, interleukin 6, and tumor necrosis factor α. Sal treatment was effective in reducing neuropathological indicators, such as amyloid-β levels and the number of apoptotic cells. When the relevant literature on the treatment of rodent AD models is combined with Sal, the therapeutic potential of Sal through multiple mechanisms was confirmed. However, further confirmation by higher quality studies, larger sample sizes, and more comprehensive outcome evaluations in clinical trials is needed in the future.

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Unbiased proteomic profiling reveals the IP3R modulator AHCYL1/IRBIT as a novel interactor of microtubule-associated protein tau

Cited by 5 publications

References 70 publications

S-adenosylhomocysteine hydrolase-like protein 1 (AHCYL1) inhibits lung cancer tumorigenesis by regulating cell plasticity

S-adenosylhomocysteine hydrolase-like protein 1 (AHCYL1) inhibits lung cancer tumorigenesis by regulating cell plasticity

Actin-nucleation promoting factor N-WASP influences alpha-synuclein condensates and pathology

Neuroprotective Mechanisms of Salidroside in Alzheimer’s Disease: A Systematic Review and Meta-analysis of Preclinical Studies

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