Using β3 integrin to control reactive astrocytes, and help neurons survive

2021 ◽  
Keyword(s):  
Reactive Astrocytes ◽  
Β3 Integrin

scholarly journals Intracellular Ca2+ Increases and Connexin 43 Hemichannel Opening Are Necessary but Not Sufficient for Thy-1-Induced Astrocyte Migration

2018 ◽  
Vol 19 (8) ◽  
pp. 2179 ◽  
Author(s):  
Raúl Lagos-Cabré ◽  
Marianne Brenet ◽  
Jorge Díaz ◽  
Ramón Pérez ◽  
Leonardo Pérez ◽  
...  
Keyword(s):  
Connexin 43 ◽  
Reactive Astrocytes ◽  
Αvβ3 Integrin ◽  
Neuronal Protein ◽  
Inflammatory Conditions ◽  
Β3 Integrin ◽  
Pre Treatment ◽  
And Migration ◽  
Necrosis Factor ◽  
Migratory Phenotype

Under pro-inflammatory conditions, astrocytes become reactive and acquire a migratory phenotype. Our results show that hemichannels formed by connexin 43 (Cx43) play an important role in Thy-1-induced astrocyte migration. The neuronal protein Thy-1 binds to αvβ3 integrin in astrocytes, thereby leading to intricate signaling pathways that include calcium (Ca2+) release from intracellular stores, opening of Cx43 hemichannels, release of ATP, activation of P2X7 receptor, and Ca2+ influx. However, because these Thy-1 effects occur exclusively in reactive astrocytes, we wondered whether by elevating calcium levels and promoting hemichannel opening we could prompt non-reactive astrocytes to respond to Thy-1. Cx43 immunoreactivity increased at juxta-membrane sites, where hemichannels (not gap junctions) participate in astrocyte polarization and migration stimulated by Thy-1. Also, intracellular Ca2+ increase, due to ionomycin treatment, induced hemichannel opening, but activated astrocyte migration only partially, and this limitation was overcome by pre-treatment with tumor necrosis factor (TNF) and Thy-1. Finally, αvβ3 integrin formed membrane clusters after TNF stimulation or overexpression of β3 integrin. We suggest that these microclusters are required for cells to respond to Thy-1 stimulation. Therefore, the large increase in intracellular Ca2+ and hemichannel opening induced by ionomycin are required, but not sufficient, to permit Thy-1-induced astrocyte migration. Thus, we suggest that proinflammatory stimuli prompt astrocytes to respond to migratory signals of neuronal cells.

scholarly journals Bi-directional network remodeling by reactive astrocytes

IBRO Reports ◽  
2019 ◽  
Vol 6 ◽  
pp. S15
Author(s):  
Schuichi Koizumi
Keyword(s):  
Reactive Astrocytes

Induction of apoptotic cell death preferentially in reactive astrocytes by concanavalin A

2009 ◽  
Vol 108 (3) ◽  
pp. 248-251 ◽  
Author(s):  
Hideki Yoshida ◽  
Kaoru Nagai
Keyword(s):  
Cell Death ◽  
Concanavalin A ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Reactive Astrocytes

scholarly journals The Key Regulator of Necroptosis, RIP1 Kinase, Contributes to the Formation of Astrogliosis and Glial Scar in Ischemic Stroke

2021 ◽  
Author(s):  
Yong-Ming Zhu ◽  
Liang Lin ◽  
Chao Wei ◽  
Yi Guo ◽  
Yuan Qin ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Glucose Deprivation ◽  
Artery Occlusion ◽  
Glial Scar ◽  
Scar Formation ◽  
Reactive Astrocytes ◽  
Interacting Protein ◽  
Protein Levels ◽  
Endothelial Growth Factor ◽  
Cerebral Artery Occlusion

AbstractNecroptosis initiation relies on the receptor-interacting protein 1 kinase (RIP1K). We recently reported that genetic and pharmacological inhibition of RIP1K produces protection against ischemic stroke-induced astrocytic injury. However, the role of RIP1K in ischemic stroke-induced formation of astrogliosis and glial scar remains unknown. Here, in a transient middle cerebral artery occlusion (tMCAO) rat model and an oxygen and glucose deprivation and reoxygenation (OGD/Re)-induced astrocytic injury model, we show that RIP1K was significantly elevated in the reactive astrocytes. Knockdown of RIP1K or delayed administration of RIP1K inhibitor Nec-1 down-regulated the glial scar markers, improved ischemic stroke-induced necrotic morphology and neurologic deficits, and reduced the volume of brain atrophy. Moreover, knockdown of RIP1K attenuated astrocytic cell death and proliferation and promoted neuronal axonal generation in a neuron and astrocyte co-culture system. Both vascular endothelial growth factor D (VEGF-D) and its receptor VEGFR-3 were elevated in the reactive astrocytes; simultaneously, VEGF-D was increased in the medium of astrocytes exposed to OGD/Re. Knockdown of RIP1K down-regulated VEGF-D gene and protein levels in the reactive astrocytes. Treatment with 400 ng/ml recombinant VEGF-D induced the formation of glial scar; conversely, the inhibitor of VEGFR-3 suppressed OGD/Re-induced glial scar formation. RIP3K and MLKL may be involved in glial scar formation. Taken together, these results suggest that RIP1K participates in the formation of astrogliosis and glial scar via impairment of normal astrocyte responses and enhancing the astrocytic VEGF-D/VEGFR-3 signaling pathways. Inhibition of RIP1K promotes the brain functional recovery partially via suppressing the formation of astrogliosis and glial scar. Graphical Abstract

scholarly journals Structural and functional analysis of LIM domain-dependent recruitment of paxillin to αvβ3 integrin-positive focal adhesions

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Marta Ripamonti ◽  
Nicolas Liaudet ◽  
Latifeh Azizi ◽  
Daniel Bouvard ◽  
Vesa P. Hytönen ◽  
...  
Keyword(s):  
Focal Adhesions ◽  
Bimolecular Fluorescence Complementation ◽  
Molecular Organization ◽  
Structural Function ◽  
Αvβ3 Integrin ◽  
Lim Domain ◽  
Dissociation Kinetics ◽  
Mechanical Coupling ◽  
Β3 Integrin

AbstractThe LIM domain-dependent localization of the adapter protein paxillin to β3 integrin-positive focal adhesions (FAs) is not mechanistically understood. Here, by combining molecular biology, photoactivation and FA-isolation experiments, we demonstrate specific contributions of each LIM domain of paxillin and reveal multiple paxillin interactions in adhesion-complexes. Mutation of β3 integrin at a putative paxillin binding site (β3VE/YA) leads to rapidly inward-sliding FAs, correlating with actin retrograde flow and enhanced paxillin dissociation kinetics. Induced mechanical coupling of paxillin to β3VE/YA integrin arrests the FA-sliding, thereby disclosing an essential structural function of paxillin for the maturation of β3 integrin/talin clusters. Moreover, bimolecular fluorescence complementation unveils the spatial orientation of the paxillin LIM-array, juxtaposing the positive LIM4 to the plasma membrane and the β3 integrin-tail, while in vitro binding assays point to LIM1 and/or LIM2 interaction with talin-head domain. These data provide structural insights into the molecular organization of β3 integrin-FAs.

Sign in / Sign up

Export Citation Format

Share Document