scholarly journals The biophysical, molecular, and anatomical landscape of pigeon CRY4: A candidate light-based quantal magnetosensor

2020 ◽  
Vol 6 (33) ◽  
pp. eabb9110
Author(s):  
Tobias Hochstoeger ◽  
Tarek Al Said ◽  
Dante Maestre ◽  
Florian Walter ◽  
Alexandra Vilceanu ◽  
...  
Keyword(s):  
Magnetic Fields ◽  
Glutamate Receptor ◽  
Molecular Mechanisms ◽  
Plexiform Layer ◽  
Horizontal Cells ◽  
Spectroscopic Methods ◽  
Glutamatergic Synapses ◽  
Radical Pairs ◽  
Interacting Protein ◽  
Tryptophan Residues

The biophysical and molecular mechanisms that enable animals to detect magnetic fields are unknown. It has been proposed that birds have a light-dependent magnetic compass that relies on the formation of radical pairs within cryptochrome molecules. Using spectroscopic methods, we show that pigeon cryptochrome clCRY4 is photoreduced efficiently and forms long-lived spin-correlated radical pairs via a tetrad of tryptophan residues. We report that clCRY4 is broadly and stably expressed within the retina but enriched at synapses in the outer plexiform layer in a repetitive manner. A proteomic survey for retinal-specific clCRY4 interactors identified molecules that are involved in receptor signaling, including glutamate receptor–interacting protein 2, which colocalizes with clCRY4. Our data support a model whereby clCRY4 acts as an ultraviolet-blue photoreceptor and/or a light-dependent magnetosensor by modulating glutamatergic synapses between horizontal cells and cones.

scholarly journals Strip1 regulates retinal ganglion cell survival by suppressing Jun-mediated apoptosis to promote retinal neural circuit formation

2021 ◽  
Author(s):  
Mai Ahmed ◽  
Yutaka Kojima ◽  
Ichiro Masai
Keyword(s):  
Molecular Mechanisms ◽  
Neural Circuit ◽  
Ganglion Cells ◽  
Plexiform Layer ◽  
Bipolar Cells ◽  
Inner Plexiform Layer ◽  
Retinal Ganglion ◽  
Interacting Protein ◽  
Retina Development ◽  
Circuit Formation

In the vertebrate retina, an interplay between retinal ganglion cells (RGCs), amacrine and bipolar cells establishes a synaptic layer called the inner plexiform layer (IPL). This circuit conveys signals from photoreceptors to visual centers in the brain. However, the molecular mechanisms involved in its development remain poorly understood. Striatin-interacting protein 1 (Strip1) is a core component of the STRIPAK complex, and it has shown emerging roles in embryonic morphogenesis. Here, we uncover the importance of Strip1 in inner retina development. Using zebrafish, we show that loss of Strip1 causes defects in IPL formation. In strip1 mutants, RGCs undergo dramatic cell death shortly after birth. Amacrine and bipolar cells subsequently invade the degenerating RGC layer, leading to a disorganized IPL. Thus, Strip1 promotes IPL formation through RGC maintenance. Mechanistically, zebrafish Strip1 interacts with its STRIPAK partner, Striatin3, to promote RGC survival by suppressing Jun-mediated apoptosis. In addition to its function in RGC maintenance, Strip1 is required for RGC dendritic patterning, which likely contributes to proper IPL formation. Taken together, we propose that a series of Strip1-mediated regulatory events coordinates inner retinal circuit formation by maintaining RGCs during development, which ensures proper positioning and neurite patterning of inner retinal neurons.

scholarly journals Polymodal Functionality of C. elegans OLL Neurons in Mechanosensation and Thermosensation

2021 ◽  
Author(s):  
Yuedan Fan ◽  
Wenjuan Zou ◽  
Jia Liu ◽  
Umar Al-Sheikh ◽  
Hankui Cheng ◽  
...  
Keyword(s):  
Glutamate Receptor ◽  
Sensory Neurons ◽  
Molecular Mechanisms ◽  
Temperature Sensitive ◽  
Cold Sensation ◽  
Cold Response ◽  
C Elegans ◽  
Sensory Modalities ◽  
A Cell ◽  
Bona Fide

AbstractSensory modalities are important for survival but the molecular mechanisms remain challenging due to the polymodal functionality of sensory neurons. Here, we report the C. elegans outer labial lateral (OLL) sensilla sensory neurons respond to touch and cold. Mechanosensation of OLL neurons resulted in cell-autonomous mechanically-evoked Ca2+ transients and rapidly-adapting mechanoreceptor currents with a very short latency. Mechanotransduction of OLL neurons might be carried by a novel Na+ conductance channel, which is insensitive to amiloride. The bona fide mechano-gated Na+-selective degenerin/epithelial Na+ channels, TRP-4, TMC, and Piezo proteins are not involved in this mechanosensation. Interestingly, OLL neurons also mediated cold but not warm responses in a cell-autonomous manner. We further showed that the cold response of OLL neurons is not mediated by the cold receptor TRPA-1 or the temperature-sensitive glutamate receptor GLR-3. Thus, we propose the polymodal functionality of OLL neurons in mechanosensation and cold sensation.

scholarly journals Identification of Nucleolin as a Novel AEG-1-Interacting Protein in Breast Cancer via Interactome Profiling

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2842
Author(s):  
Seong-Jae Lee ◽  
Kyoung-Min Choi ◽  
Geul Bang ◽  
Seo-Gyu Park ◽  
Eun-Bi Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Cells ◽  
Molecular Mechanisms ◽  
Affinity Purification ◽  
Ectopic Expression ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Interacting Protein ◽  
Proliferation And Invasion ◽  
Oncogenic Function

Breast cancer is one of the most common malignant diseases worldwide. Astrocyte elevated gene-1 (AEG-1) is upregulated in breast cancer and regulates breast cancer cell proliferation and invasion. However, the molecular mechanisms by which AEG-1 promotes breast cancer have yet to be fully elucidated. In order to delineate the function of AEG-1 in breast cancer development, we mapped the AEG-1 interactome via affinity purification followed by LC-MS/MS. We identified nucleolin (NCL) as a novel AEG-1 interacting protein, and co-immunoprecipitation experiments validated the interaction between AEG-1 and NCL in breast cancer cells. The silencing of NCL markedly reduced not only migration/invasion, but also the proliferation induced by the ectopic expression of AEG-1. Further, we found that the ectopic expression of AEG-1 induced the tyrosine phosphorylation of c-Met, and NCL knockdown markedly reduced this AEG-1 mediated phosphorylation. Taken together, our report identifies NCL as a novel mediator of the oncogenic function of AEG-1, and suggests that c-Met could be associated with the oncogenic function of the AEG-1-NCL complex in the context of breast cancer.

scholarly journals Disruption of Glutamate Receptor-Interacting Protein in Nucleus Accumbens Enhances Vulnerability to Cocaine Relapse

2013 ◽  
Vol 39 (3) ◽  
pp. 759-769 ◽  
Author(s):  
Lisa A Briand ◽  
Blake A Kimmey ◽  
Pavel I Ortinski ◽  
Richard L Huganir ◽  
R Christopher Pierce
Keyword(s):  
Nucleus Accumbens ◽  
Glutamate Receptor ◽  
Interacting Protein

scholarly journals Long-Lasting Alterations in Gene Expression of Postsynaptic Density 95 and Inotropic Glutamatergic Receptor Subunit in the Mesocorticolimbic System of Rat Offspring Born to Morphine-Addicted Mothers

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Pei-Ling Wu ◽  
Yung-Ning Yang ◽  
Jau-Ling Suen ◽  
Yu-Chen S. H. Yang ◽  
Chun-Hwa Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nmda Receptor ◽  
Glutamate Receptor ◽  
Ampa Receptor ◽  
Prenatal Exposure ◽  
Molecular Mechanisms ◽  
Postsynaptic Density ◽  
Receptor Subunit ◽  
Rat Offspring ◽  
Ampa Receptor Subunit

Prenatal exposure to morphine causes altered glutamatergic neurotransmission, which plays an important pathophysiological role for neurobiological basis of opiate-mediated behaviors in such offspring. However, it is still not clear whether such alteration involves gene expression of ionotropic glutamate receptor subunits. In this study, we further studied whether prenatal morphine exposure resulted in long-term changes in the gene expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, N-methyl-d-aspartate (NMDA) receptor, and postsynaptic density 95 in the mesocorticolimbic area (an essential integration circuitry for drug craving behavior), nucleus accumbens (NAc), ventral tegmental area (VTA), and prefrontal cortex (PFC), of rat offspring from morphine-addicted mothers. Experimental results showed that prenatal morphine exposure led to a persistent downregulation of gene expression in the AMPA and NMDA receptor subunit, with a differential manner of decreased magnitudes, at the age of postnatal days 14 (P14) and P30. However, in PFC, the gene expression of the AMPA receptor subunit was not synchronized in observed rat offspring subjected to prenatal morphine exposure. An upregulation of gene expression in the AMPA receptor subunit 3 (GluR3) was persistently observed at P14 and P30. Furthermore, the gene expressions of PSD-95 in NAc, VTA, and PFC were all decreased concurrently. Collectively, the results suggest that prenatal exposure to morphine may initiate molecular mechanisms leading to a long-lasting, differential alteration in gene expression of the inotropic glutamate receptor subunit and PSD-95 in the mesocorticolimbic circuitry in rat offspring. This study raises a possibility in which differential changes in gene expression with a long-lasting manner may play a role for the development of nearly permanent changes in opiate-mediated behaviors, at least in part for the neurobiological pathogenesis in offspring.

scholarly journals RIPK1 promotes death receptor-independent caspase-8-mediated apoptosis under unresolved ER stress conditions

2014 ◽  
Vol 5 (12) ◽  
pp. e1555-e1555 ◽  
Author(s):  
Y Estornes ◽  
M A Aguileta ◽  
C Dubuisson ◽  
J De Keyser ◽  
V Goossens ◽  
...  
Keyword(s):  
Er Stress ◽  
Molecular Mechanisms ◽  
Death Receptor ◽  
Caspase 8 ◽  
Interacting Protein ◽  
Life And Death ◽  
Unfolded Protein ◽  
Induced Apoptosis ◽  
The Unfolded Protein Response ◽  
Protein Response

Abstract Accumulation of unfolded proteins in the endoplasmic reticulum (ER) causes ER stress and results in the activation of the unfolded protein response (UPR), which aims at restoring ER homeostasis. However, when the stress is too severe the UPR switches from being a pro-survival response to a pro-death one, and the molecular mechanisms underlying ER stress-mediated death have remained incompletely understood. In this study, we identified receptor interacting protein kinase 1 (RIPK1)—a kinase at the crossroad between life and death downstream of various receptors—as a new regulator of ER stress-induced death. We found that Ripk1-deficient MEFs are protected from apoptosis induced by ER stressors, which is reflected by reduced caspase activation and PARP processing. Interestingly, the pro-apoptotic role of Ripk1 is independent of its kinase activity, is not regulated by its cIAP1/2-mediated ubiquitylation, and does not rely on the direct regulation of JNK or CHOP, two reportedly main players in ER stress-induced death. Instead, we found that ER stress-induced apoptosis in these cells relies on death receptor-independent activation of caspase-8, and identified Ripk1 upstream of caspase-8. However, in contrast to RIPK1-dependent apoptosis downstream of TNFR1, we did not find Ripk1 associated with caspase-8 in a death-inducing complex upon unresolved ER stress. Our data rather suggest that RIPK1 indirectly regulates caspase-8 activation, in part via interaction with the ER stress sensor inositol-requiring protein 1 (IRE1).

scholarly journals SGTA associates with intracellular aggregates in neurodegenerative diseases.

2020 ◽  
Author(s):  
Shun Kubota ◽  
Hiroshi Doi ◽  
Shigeru Koyano ◽  
Kenichi Tanaka ◽  
Shingo Ikeda ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Molecular Mechanisms ◽  
In Vitro Study ◽  
Interacting Proteins ◽  
Interacting Protein ◽  
Cytoplasmic Inclusions ◽  
Specific Proteins ◽  
Intracellular Aggregates ◽  
Polyq Diseases

Abstract Intracellular aggregates are a common pathological hallmark of neurodegenerative diseases such as polyglutamine (polyQ) diseases, amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), and multiple system atrophy (MSA). Aggregates are mainly formed by aberrant disease-specific proteins and are accompanied by accumulation of other aggregate-interacting proteins. Although aggregate-interacting proteins have been considered to modulate the formation of aggregates and to be involved in molecular mechanisms of disease progression, the components of aggregate-interacting proteins remain unknown. In this study, we showed that small glutamine-rich tetratricopeptide repeat-containing protein alfa (SGTA) is an aggregate-interacting protein in neurodegenerative diseases. Immunohistochemistry showed that SGTA interacted with intracellular aggregates in Huntington disease (HD) cell models and neurons of HD model mice. We also revealed that SGTA colocalized with intracellular aggregates in postmortem brains of patients with polyQ diseases including spinocerebellar ataxia (SCA)1, SCA2, SCA3, and dentatorubral–pallidoluysian atrophy. In addition, SGTA colocalized with glial cytoplasmic inclusions in the brains of MSA patients, whereas no accumulation of SGTA was observed in neurons of PD and ALS patients. In vitro study showed that SGTA bound to polyQ aggregates through its C-terminal domain and SGTA overexpression reduced intracellular aggregates. These results suggest that SGTA may play a role in the formation of aggregates and may act as potential modifier of molecular pathological mechanisms of polyQ diseases and MSA.

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