bims-nocaut 2023-06-04 papers

Issue of 2023–06–04
three papers selected by
Quentin Frenger, University of Strasbourg

Autophagy. 2023 May 31. 1-3

An emerging role of non-canonical conjugation of ATG8 proteins in plant response to heat stress.

Xuanang Zheng, Siyu Chen, Caiji Gao, Jun Zhou.

Members of the ATG8 (autophagy-related protein 8) protein family can be non-canonically conjugated to single membrane-bound organelles. The exact function of ATG8 on these single membranes remains poorly understood. Recently, using Arabidopsis thaliana as a model system, we identified a non-canonical conjugation of ATG8 pathway involved in the reconstruction of the Golgi apparatus upon heat stress. Short acute heat stress resulted in rapid vesiculation of the Golgi, which was accompanied with the translocation of ATG8 proteins (ATG8a to ATG8i) to the dilated cisternae. More importantly, we found that ATG8 proteins can recruit clathrin to facilitate Golgi reassembly by stimulating the budding of ATG8-positive vesicles from dilated cisternae. These findings provide new insight into one of the possible functions of ATG8 translocation onto single membrane organelles, and will contribute to a better understanding of non-canonical conjugation of ATG8 in eukaryotic cells.Abbreviations: ADS, AIMs docking site; AIM, ATG8-interacting motif; ATG, autophagy-related; CLC2, Clathrin light chain 2; ConcA, concanamycin A; HS, heat stress; PE, phosphatidylethanolamine; PM, plasma membrane; PS, phosphatidylserine; TGN, trans-Golgi network; V-ATPase, vacuolar-type ATPase.

Keywords: ATG8; Golgi; clathrin; heat stress; non-canonical autophagy; vacuole

DOI: https://doi.org/10.1080/15548627.2023.2219161

Nat Commun. 2023 May 29. 14(1): 3077

LC3-associated phagocytosis promotes glial degradation of axon debris after injury in Drosophila models.

Áron Szabó, Virág Vincze, Aishwarya Sanjay Chhatre, András Jipa, Sarolta Bognár, Katalin Eszter Varga, Poulami Banik, Adél Harmatos-Ürmösi, Lukas J Neukomm, Gábor Juhász.

Glial engulfment of neuron-derived debris after trauma, during development, and in neurodegenerative diseases supports nervous system functions. However, mechanisms governing the efficiency of debris degradation in glia have remained largely unexplored. Here we show that LC3-associated phagocytosis (LAP), an engulfment pathway assisted by certain autophagy factors, promotes glial phagosome maturation in the Drosophila wing nerve. A LAP-specific subset of autophagy-related genes is required in glia for axon debris clearance, encoding members of the Atg8a (LC3) conjugation system and the Vps34 lipid kinase complex including UVRAG and Rubicon. Phagosomal Rubicon and Atg16 WD40 domain-dependent conjugation of Atg8a mediate proper breakdown of internalized axon fragments, and Rubicon overexpression in glia accelerates debris elimination. Finally, LAP promotes survival following traumatic brain injury. Our results reveal a role of glial LAP in the clearance of neuronal debris in vivo, with potential implications for the recovery of the injured nervous system.

DOI: https://doi.org/10.1038/s41467-023-38755-4

Adv Sci (Weinh). 2023 May 28. e2206432

Bone Marrow Mesenchymal Stem Cell-Derived Dermcidin-Containing Migrasomes enhance LC3-Associated Phagocytosis of Pulmonary Macrophages and Protect against Post-Stroke Pneumonia.

Tiemei Li, Xiaotao Su, Pinglan Lu, Xinmei Kang, Mengyan Hu, Chunyi Li, Shisi Wang, Danli Lu, Shishi Shen, Huipeng Huang, Yuxin Liu, Xiaohui Deng, Wei Cai, Lei Wei, Zhengqi Lu.

Pneumonia is one of the leading causes of death in patients with acute ischemic stroke (AIS). Antibiotics fail to improve prognosis of patients with post-stroke pneumonia, albeit suppressing infection, due to adverse impacts on the immune system. The current study reports that bone marrow mesenchymal stem cells (BM-MSC) downregulate bacterial load in the lungs of stroke mice models. RNA-sequencing of the lung from BM-MSC-treated stroke models indicates that BM-MSC modulates pulmonary macrophage activities after cerebral ischemia. Mechanistically, BM-MSC promotes the bacterial phagocytosis of pulmonary macrophages through releasing migrasomes, which are migration-dependent extracellular vesicles. With liquid chromatography-tandem mass spectrometry (LC-MS/MS), the result shows that BM-MSC are found to load the antibacterial peptide dermcidin (DCD) in migrasomes upon bacterial stimulation. Besides the antibiotic effect, DCD enhances LC3-associated phagocytosis (LAP) of macrophages, facilitating their bacterial clearance. The data demonstrate that BM-MSC is a promising therapeutic candidate against post-stroke pneumonia, with dual functions of anti-infection and immunol modulation, which is more than a match for antibiotics treatment.

Keywords: bone marrow mesenchymal stem cell; macrophage; migrasome; post-stroke pneumonia

DOI: https://doi.org/10.1002/advs.202206432