Beyond Atg8 binding: The role of AIM/LIR motifs in autophagy

Fracchiolla, Dorotea; Sawa-Makarska, Justyna; Martens, Sascha

doi:10.1080/15548627.2016.1277311

Cited by 33 publications

(22 citation statements)

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“…ATG8 conjugates to the membrane lipid phosphatidylethanolamine present in autophagosomal membranes. ATG8 also functions in the selective fusion of autophagosome with the vacuole, and various intracellular processes not associated with autophagy [36][37][38][39] . ATG8 upregulation suggests that selective autophagy increases to remove excess biomacromolecules or organelles during the encystment.…”

Section: Discussionmentioning

confidence: 99%

Novel insights into molecular mechanisms of Pseudourostyla cristata encystment using comparative transcriptomics

Pan

Niu

Bhatti

et al. 2019

Sci Rep

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The encystment of many ciliates is an advanced survival strategy against adversity and the most important reason for ciliates existence worldwide. However, the molecular mechanism for the encystment of free-living ciliates is poorly understood. Here, we performed comparative transcriptomic analysis of dormant cysts and trophonts from Pseudourostyla cristata using transcriptomics, qRT-PCR and bioinformatic techniques. We identified 2565 differentially expressed unigenes between the dormant cysts and the trophonts. The total number of differentially expressed genes in GO database was 1752. The differential unigenes noted to the GO terms were 1993. These differential categories were mainly related to polyamine transport, pectin decomposition, cytoplasmic translation, ribosome, respiratory chain, ribosome structure, ion channel activity, and RNA ligation. A total of 224 different pathways were mapped. Among them, 184 pathways were upregulated, while 162 were downregulated. Further investigation showed that the calcium and AMPK signaling pathway had important induction effects on the encystment. In addition, FOXO and ubiquitin-mediated proteolysis signaling pathway jointly regulated the encystment. Based on these findings, we propose a hypothetical signaling network that regulates Pseudourostyla cristata encystment. Overall, these results provide deeper insights into the molecular mechanisms of ciliates encystment and adaptation to adverse environments.of Strepkiella histriomuscorum has been studied in the encystment and trophont stages through biochip technology, which suggested that cyst formation is associated with Ribosomal L7, Ribosomal acidic P2, Cathepsin B, Cathepsin H, Ubiquitin, Ca 2+ -ATPase and Actin1 7 . Other studies investigated the differential proteins of the cysts and the trophonts from Pseudourostyla cristata (P. cristata) using shotgun LC-MS/MS, finding the association of fibrillarin-like rRNA methylase, methylmalonyl-coenzyme mutase, ADP ribosylation factor, Rab12, MAPK-related kinase and KR multi-domain proteins with cyst formation 8 . However, the reports of systematically studying the genes and signaling pathways involved in the formation of ciliate cysts at the molecular level are rare 8 . In this study, we have investigated the molecular mechanism underlying the cyst formation in ciliates using comparative transcriptomic analysis, quantitative real-time PCR (qRT-PCR) and bioinformatic techniques. Furthermore, we have focused on the analysis of several important signaling pathways related to the encystment. Therefore, we have proposed a hypothetical network that regulates Pseudourostyla cristata encystment. Our study generates novel insights into the molecular mechanisms of the cyst formation in free-living ciliates.www.nature.com/scientificreports www.nature.com/scientificreports/ dormant cysts of P. cristata (Fig. 4). Validation of results by transcriptome sequencing showed that mRNA outcomes were consistent with the transcriptomic data of trophonts and dormant cysts in P. cristata (Fig. 4).

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Section: Discussionmentioning

confidence: 99%

Novel insights into molecular mechanisms of Pseudourostyla cristata encystment using comparative transcriptomics

Pan

Niu

Bhatti

et al. 2019

Sci Rep

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“…In contrast, the HP2 pocket of LC3B includes the hydrophobic side chains of F52, V54, P55, L63, I66, and I67 (Noda et al, 2008;Kuang et al, 2016). These residues provide the platform for hydrophobic, electrostatic and hydrogen bond interactions with LIR-containing proteins (Birgisdottir et al, 2013;Fracchiolla et al, 2017;Wirth et al, 2019). Besides the two hydrophobic pockets, there are other two important conserved regions on the ATG8 structure, called the LDK tripeptide (i.e., L47, D48, and K49) and the ubiquitin patch (L8-I44-V70), which are located in the front and back of the HP1 and HP2 pocket, respectively.…”

Section: Structure Of Atg8 Family Membersmentioning

confidence: 99%

Structure and Dynamics in the ATG8 Family From Experimental to Computational Techniques

Sora

Kumar

Maiani

et al. 2020

Front. Cell Dev. Biol.

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Autophagy is a conserved and essential intracellular mechanism for the removal of damaged components. Since autophagy deregulation is linked to different kinds of pathologies, it is fundamental to gain knowledge on the fine molecular and structural details related to the core proteins of the autophagy machinery. Among these, the family of human ATG8 proteins plays a central role in recruiting other proteins to the different membrane structures involved in the autophagic pathway. Several experimental structures are available for the members of the ATG8 family alone or in complex with their different biological partners, including disordered regions of proteins containing a short linear motif called LC3 interacting motif. Recently, the first structural details of the interaction of ATG8 proteins with biological membranes came into light. The availability of structural data for human ATG8 proteins has been paving the way for studies on their structure-function-dynamic relationship using biomolecular simulations. Experimental and computational structural biology can help to address several outstanding questions on the mechanism of human ATG8 proteins, including their specificity toward different interactors, their association with membranes, the heterogeneity of their conformational ensemble, and their regulation by post-translational modifications. We here summarize the main results collected so far and discuss the future perspectives within the field and the knowledge gaps. Our review can serve as a roadmap for future structural and dynamics studies of the ATG8 family members in health and disease.

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“…54 Selective autophagy is triggered by various stimuli, and special cargoes are tagged by ubiquitination and sent to phagophores. 27,56,57 The selectivity of selective autophagy relies on receptors such as p62/SQSTM1 and its interaction with ubiquitin-like proteins through ubiquitin-like modifiers (UBLs), which recognize, target, and degrade specific cargoes. 27,56,57 The selectivity of selective autophagy relies on receptors such as p62/SQSTM1 and its interaction with ubiquitin-like proteins through ubiquitin-like modifiers (UBLs), which recognize, target, and degrade specific cargoes.…”

Section: The Novel Regulatory Mechanisms Of Atm In Selective Autophagymentioning

confidence: 99%

“…55 During this process, proteins with the LC3 interacting regions in mammals (LIR) and Atg8 interacting motifs in yeast (AIM) are indispensable in bringing the organelles to autophagosomes. 27,56,57 The selectivity of selective autophagy relies on receptors such as p62/SQSTM1 and its interaction with ubiquitin-like proteins through ubiquitin-like modifiers (UBLs), which recognize, target, and degrade specific cargoes. 53,55,58 In addition, UBLs have been demonstrated to directly engage the autophagosome nucleation machinery.…”

Section: The Novel Regulatory Mechanisms Of Atm In Selective Autophagymentioning

confidence: 99%

Multifaceted roles of ATM in autophagy: From nonselective autophagy to selective autophagy

Liang

Liu

et al. 2019

Cell Biochemistry & Function

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The ataxia-telangiectasia mutated (ATM) protein kinase is best known for its critical nuclear roles in the DNA damage response (DDR), cell cycle checkpoints, and the maintenance of gene stability. In this review, we highlight the multifaceted cytoplasmic functions of ATM in autophagy. We focused on the functions of ATM in nonselective autophagy in cancer. An Oncomine database analysis showed a tight association between ATM and autophagy in various cancers. In particular, its mechanisms in nonselective autophagy, those induced by ionizing radiation (IR), are illustrated in detail and involve the MAPK14 pathway, mTOR pathway, and Beclin1/PI3KIII complexes. Recently, an increasing number of studies revealed that autophagy could also be highly selective. We additionally emphasized the novel roles of ATM in selective autophagy, including mitophagy, pexophagy, and lipophagy. The regulation of these processes mainly involves ATM-PEX5, ATM-AMPK-TSC2-mTORC1-ULK1, PPM1D-ATM-MTOR, PINK I/Parkin, and NAD+/ SIRT1. We aimed to provide new perspectives on the importance of ATM in the diverse field of autophagy. The intricate regulation of ATM in autophagy still requires further investigation, which would enhance our understanding of its role in cell dynamics and homeostasis.Significance of the study Our review highlighted the multifaceted cytoplasmic functions of ATM on autophagy. First, we focused on the functions of ATM in nonselective autophagy within cancer especially those induced by IR, involving the MAPK14 pathway, mTOR pathway, and Beclin1/PI3KIII complexes. These provided a theoretical understanding of tumour radiosensitivity and chemosensitivity. In addition, we emphasized the novel roles of ATM in selective autophagy, including mitophagy, pexophagy, and lipophagy. This review provides new perspectives on the importance of ATM in the diverse field of autophagy, which would provide more information on its role in whole cell dynamics and homeostasis.

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Beyond Atg8 binding: The role of AIM/LIR motifs in autophagy

Cited by 33 publications

References 0 publications

Novel insights into molecular mechanisms of Pseudourostyla cristata encystment using comparative transcriptomics

Novel insights into molecular mechanisms of Pseudourostyla cristata encystment using comparative transcriptomics

Structure and Dynamics in the ATG8 Family From Experimental to Computational Techniques

Multifaceted roles of ATM in autophagy: From nonselective autophagy to selective autophagy

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