Faculty Opinions recommendation of Spatial control of avidity regulates initiation and progression of selective autophagy.

Author(s):  
Michael J Ragusa
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
David M. Hollenstein ◽  
Mariya Licheva ◽  
Nicole Konradi ◽  
David Schweida ◽  
Hector Mancilla ◽  
...  

AbstractAutophagosomes form at the endoplasmic reticulum in mammals, and between the vacuole and the endoplasmic reticulum in yeast. However, the roles of these sites and the mechanisms regulating autophagosome formation are incompletely understood. Vac8 is required for autophagy and recruits the Atg1 kinase complex to the vacuole. Here we show that Vac8 acts as a central hub to nucleate the phagophore assembly site at the vacuolar membrane during selective autophagy. Vac8 directly recruits the cargo complex via the Atg11 scaffold. In addition, Vac8 recruits the phosphatidylinositol 3-kinase complex independently of autophagy. Cargo-dependent clustering and Vac8-dependent sequestering of these early autophagy factors, along with local Atg1 activation, promote phagophore assembly site assembly at the vacuole. Importantly, ectopic Vac8 redirects autophagosome formation to the nuclear membrane, indicating that the vacuolar membrane is not specifically required. We propose that multiple avidity-driven interactions drive the initiation and progression of selective autophagy.


2010 ◽  
Author(s):  
Cynthia Fast ◽  
Dennis Garlick ◽  
Aaron P. Blaisdell

2017 ◽  
Vol 5 (2) ◽  
pp. 215-226
Author(s):  
Kurdish Studies

Andrea Fischer-Tahir and Sophie Wagenhofer (edsF), Disciplinary Spaces: Spatial Control, Forced Assimilation and Narratives of Progress since the 19th Century, Bielefeld: Transcript Verlag, 2017, 300 pp., (ISBN: 978-3-8376-3487-7).Ayşegül Aydın and Cem Emrence, Zones of Rebellion: Kurdish Insurgents and the Turkish State, Ithaca and London: Cornell University Press, 2015, 192 pp., (ISBN: 978-0-801-45354-0).Evgenia I. Vasil’eva, Yugo-Vostochniy Kurdistan v XVI-XIX vv. Istochnik po Istorii Kurdskikh Emiratov Ardelan i Baban. [South-Eastern Kurdistan in the XVI-XIXth cc. A Source for the Study of Kurdish Emirates of Ardalān and Bābān], St Petersburg: Nestor-Istoria, 2016. 176 pp., (ISBN 978-5-4469-0775-5).Karin Mlodoch, The Limits of Trauma Discourse: Women Anfal Survivors in Kurdistan-Iraq, Berlin: Klaus Schwarz Verlag, 2014, 541 pp., (ISBN: 978-3-87997-719-2). 


2020 ◽  
Author(s):  
R. Kevin Tindell ◽  
Lincoln Busselle ◽  
Julianne Holloway

<div>Musculoskeletal interfacial tissues consist of complex gradients in structure, cell phenotype, and biochemical signaling that are important for function. Designing tissue engineering strategies to mimic these types of gradients is an ongoing challenge. In particular, new fabrication techniques that enable precise spatial control over fiber alignment are needed to better mimic the structural gradients present in interfacial tissues, such as the tendon-bone interface. Here, we report a modular approach to spatially controlling fiber alignment using magnetically-assisted electrospinning. Electrospun fibers were highly aligned in the presence of a magnetic field and smoothly transitioned to randomly aligned fibers away from the magnetic field. Importantly, magnetically-assisted electrospinning allows for spatial control over fiber alignment at sub-millimeter resolution along the length of the fibrous scaffold similar to the native structural gradient present in many interfacial tissues. The versatility of this approach was further demonstrated using multiple electrospinning polymers and different magnet configurations to fabricate complex fiber alignment gradients. As expected, cells seeded onto gradient fibrous scaffolds were elongated and aligned on the aligned fibers and did not show a preferential alignment on the randomly aligned fibers. Overall, this fabrication approach represents an important step forward in creating gradient fibrous materials and are promising as tissue-engineered scaffolds for regenerating functional musculoskeletal interfacial tissues. <br></div>


2020 ◽  
Author(s):  
R. Kevin Tindell ◽  
Lincoln Busselle ◽  
Julianne Holloway

<div>Musculoskeletal interfacial tissues consist of complex gradients in structure, cell phenotype, and biochemical signaling that are important for function. Designing tissue engineering strategies to mimic these types of gradients is an ongoing challenge. In particular, new fabrication techniques that enable precise spatial control over fiber alignment are needed to better mimic the structural gradients present in interfacial tissues, such as the tendon-bone interface. Here, we report a modular approach to spatially controlling fiber alignment using magnetically-assisted electrospinning. Electrospun fibers were highly aligned in the presence of a magnetic field and smoothly transitioned to randomly aligned fibers away from the magnetic field. Importantly, magnetically-assisted electrospinning allows for spatial control over fiber alignment at sub-millimeter resolution along the length of the fibrous scaffold similar to the native structural gradient present in many interfacial tissues. The versatility of this approach was further demonstrated using multiple electrospinning polymers and different magnet configurations to fabricate complex fiber alignment gradients. As expected, cells seeded onto gradient fibrous scaffolds were elongated and aligned on the aligned fibers and did not show a preferential alignment on the randomly aligned fibers. Overall, this fabrication approach represents an important step forward in creating gradient fibrous materials and are promising as tissue-engineered scaffolds for regenerating functional musculoskeletal interfacial tissues. <br></div>


EMBO Reports ◽  
2011 ◽  
Vol 12 (2) ◽  
pp. 149-156 ◽  
Author(s):  
Martin Gamerdinger ◽  
A Murat Kaya ◽  
Uwe Wolfrum ◽  
Albrecht M Clement ◽  
Christian Behl

2021 ◽  
Vol 7 (4) ◽  
pp. eabc5539
Author(s):  
Xing Li ◽  
Qian Xia ◽  
Meng Mao ◽  
Huijuan Zhou ◽  
Lu Zheng ◽  
...  

Annexin-A1 (ANXA1) has recently been proposed to play a role in microglial activation after brain ischemia, but the underlying mechanism remains poorly understood. Here, we demonstrated that ANXA1 is modified by SUMOylation, and SUMOylated ANXA1 could promote the beneficial phenotype polarization of microglia. Mechanistically, SUMOylated ANXA1 suppressed nuclear factor κB activation and the production of proinflammatory mediators. Further study revealed that SUMOylated ANXA1 targeted the IκB kinase (IKK) complex and selectively enhanced IKKα degradation. Simultaneously, we detected that SUMOylated ANXA1 facilitated the interaction between IKKα and NBR1 to promote IKKα degradation through selective autophagy. Further work revealed that the overexpression of SUMOylated ANXA1 in microglia/macrophages resulted in marked improvement in neurological function in a mouse model of cerebral ischemia. Collectively, our study demonstrates a previously unidentified mechanism whereby SUMOylated ANXA1 regulates microglial polarization and strongly indicates that up-regulation of ANXA1 SUMOylation in microglia may provide therapeutic benefits for cerebral ischemia.


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