LC3C, Bound Selectively by a Noncanonical LIR Motif in NDP52, Is Required for Antibacterial Autophagy

Muhlinen, Natalia von; Akutsu, Masato; Ravenhill, Benjamin J.; Foeglein, Ágnes; Bloor, Stuart; Rutherford, Trevor J.; Freund, Stefan; Komander, David; Randow, Felix

doi:10.1016/j.molcel.2012.08.024

Cited by 292 publications

(309 citation statements)

References 58 publications

Supporting

Mentioning

296

Contrasting

Unclassified

Order By: Relevance

“…Binding of ALFY to GABARAP facilitates the recruitment of LC3B to ALFY and p62-positive structures, further indicating that a high-affinity LIR-Atg8 protein interaction is required for exclusive autophagy. In line with this, interaction of the ubiquitin-binding autophagy receptor NDP52 (also known as CALCOCO2) with LC3C was found to be required for the recruitment of other Atg8 family members to cytosolic Salmonella Typhimurium (von Muhlinen et al, 2012). Taken together, these studies suggest that an initial interaction between an Atg8 protein and a LIR-containing receptor forms a platform for further phagophore expansion and cargo sequestration.…”

Section: Membrane Modeling In Selective Autophagymentioning

confidence: 58%

Membrane dynamics in autophagosome biogenesis

Carlsson

Simonsen

2015

Journal of Cell Science

188

169

View full text Add to dashboard Cite

Bilayered phospholipid membranes are vital to the organization of the living cell. Based on fundamental principles of polarity, membranes create borders allowing defined spaces to be encapsulated. This compartmentalization is a prerequisite for the complex functional design of the eukaryotic cell, yielding localities that can differ in composition and operation. During macroautophagy, cytoplasmic components become enclosed by a growing double bilayered membrane, which upon closure creates a separate compartment, the autophagosome. The autophagosome is then primed for fusion with endosomal and lysosomal compartments, leading to degradation of the captured material. A large number of proteins have been found to be essential for autophagy, but little is known about the specific lipids that constitute the autophagic membranes and the membrane modeling events that are responsible for regulation of autophagosome shape and size. In this Commentary, we review the recent progress in our understanding of the membrane shaping and remodeling events that are required at different steps of the autophagy pathway.This article is part of a Focus on Autophagosome biogenesis. For further reading, please see related articles: 'ERES: sites for autophagosome biogenesis and maturation?' by Jana SanchezWandelmer et al. (J. Cell Sci. 128,(185)(186)(187)(188)(189)(190)(191)(192) and 'WIPI proteins: essential PtdIns3P effectors at the nascent autophagosome' by Tassula Proikas-Cezanne et al. (J. Cell Sci. 128,(207)(208)(209)(210)(211)(212)(213)(214)(215)(216)(217).

show abstract

Section: Membrane Modeling In Selective Autophagymentioning

confidence: 58%

Membrane dynamics in autophagosome biogenesis

Carlsson

Simonsen

2015

Journal of Cell Science

188

169

View full text Add to dashboard Cite

show abstract

“…The amount of LC3-II becomes a marker for the formation of autophagosomes. The recent study performed on human cells infected with S. Typhimurium, showed that LC3C was required for antibacterial autophagy because in its absence the remaining ATG8 orthologs did not support efficient autophagy of intracellular bacteria [61]. The subsequent reports indicated that differential involvement of LC3 paralogs, LC3-II and LC3C, can classify autophagy in two separate programs that execute either pro-or anti-tumorigenic activities in renal cell carcinoma cells [62,63].…”

Section: Autophagy Signal Transduction and Corresponding Morphologicamentioning

confidence: 99%

Crosstalk between autophagy and proteasome protein degradation systems: possible implications for cancer therapy

Wójcik

2014

Folia Histochem Cytobiol.

View full text Add to dashboard Cite

Abstract:The Ubiquitin-Proteasomes System (UPS) and autophagy, two main intracellular protein degradation pathways within the eukaryotic cells which were originally regarded as rather independent, seem to be very closely related. Proteasome inhibitors, including the multipathway inhibitor bortezomib, are drawing increased attention for their therapeutic potential in the treatment of chronic inflammation and cancer, especially tumours with a high degree of malignancy. The over-activation of autophagy induces cell death and may act as a powerful tumour-suppressing mechanism. However, autophagy, serving as an important mechanism to generate nutrients in time of cellular stresses, may directly contribute to the survival of cells treated with proteasome inhibitors, and in consequence, may decrease the effectiveness of therapy. Results of studies performed on several cancer cell lines demonstrated synergy between proteasome inhibitors and autophagy inhibitors. Those results became the base for ongoing clinical trials investigating autophagy inhibition in combination with anti-cancer therapies, including bortezomib. This review provides summary of the latest data on the functioning of the UPS and the mechanisms of autophagy. The new insights describing the main pathways of autophagy activation in response to UPS inhibition related to: (i) Unfolded Protein Response, (ii) PI3K/Akt/mTOR pathway, and (iii) formation of aggresomes, are discussed. It is concluded that concomitant inhibition of the two main cellular protein degradation systems may provide new therapeutic modalities for cancer treatment.

show abstract

“…20,[30][31][32] Recently, a noncanonical LIR motif, which solely comprises 3 consecutive hydrophobic residues (LVV), has been found in the autophagy receptor CALCOCO2/NDP52. 33 This atypical LIR motif (termed as CLIR) exclusively interacts with the Atg8-family member, LC3C, and endows CALCOCO2 with a unique function in xenophagy. 33 Although the LIR-mediated interactions of Atg8-family proteins with LIR-containing proteins involved in autophagosome biogenesis and autophagic cargoes recruitment are well characterized, no relevant detailed information related to autophagic vesicle trafficking has been available yet.…”

Section: Introductionmentioning

confidence: 99%

Structural basis of FYCO1 and MAP1LC3A interaction reveals a novel binding mode for Atg8-family proteins

Cheng¹,

Wang²,

Gong³

et al. 2016

Autophagy

View full text Add to dashboard Cite

FYCO1 (FYVE and coiled-coil domain containing 1) functions as an autophagy adaptor in directly linking autophagosomes with the microtubule-based kinesin motor, and plays an essential role in the microtubule plus end-directed transport of autophagic vesicles. The specific association of FYCO1 with autophagosomes is mediated by its interaction with Atg8-family proteins decorated on the outer surface of autophagosome. However, the mechanistic basis governing the interaction between FYCO1 and Atg8-family proteins is largely unknown. Here, using biochemical and structural analyses, we demonstrated that FYCO1 contains a unique LC3-interacting region (LIR), which discriminately binds to mammalian Atg8 orthologs and preferentially binds to the MAP1LC3A and MAP1LC3B. In addition to uncovering the detailed molecular mechanism underlying the FYCO1 LIR and MAP1LC3A interaction, the determined FYCO1-LIR-MAP1LC3A complex structure also reveals a unique LIR binding mode for Atg8-family proteins, and demonstrates, first, the functional relevance of adjacent sequences C-terminal to the LIR core motif for binding to Atg8-family proteins. Taken together, our findings not only provide new mechanistic insight into FYCO1-mediated transport of autophagosomes, but also expand our understanding of the interaction modes between LIR motifs and Atg8-family proteins in general.

show abstract

LC3C, Bound Selectively by a Noncanonical LIR Motif in NDP52, Is Required for Antibacterial Autophagy

Cited by 292 publications

References 58 publications

Membrane dynamics in autophagosome biogenesis

Membrane dynamics in autophagosome biogenesis

Crosstalk between autophagy and proteasome protein degradation systems: possible implications for cancer therapy

Structural basis of FYCO1 and MAP1LC3A interaction reveals a novel binding mode for Atg8-family proteins

Contact Info

Product

Resources

About