Cargo binding to Atg19 unmasks additional Atg8 binding sites to mediate membrane–cargo apposition during selective autophagy

Sawa-Makarska, Justyna; Abert, Christine; Romanov, Julia; Zens, Bettina; Ibiricu, Iosune; Martens, Sascha

doi:10.1038/ncb2935

Cited by 102 publications

(142 citation statements)

References 37 publications

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“…Thus, some property of membrane association changes the protein reactivity of these autophagosome markers. It appears that the increased surface density of these proteins may be sufficient to specifically capture cytosolic proteins harboring many low affinity LC3/Atg8 interaction sites 40 , and possibly to alter the activity of membrane targeted enzymes 41 , and thus local concentrations of these proteins are clearly important. Whether actual oligomers are forming however has been uncertain.…”

Section: Resultsmentioning

confidence: 99%

GABARAP Like-1 enrichment on membranes: Direct observation of trans-homo-oligomerization between membranes and curvature-dependent partitioning into membrane tubules

Motta¹,

Nguyen

Gardavot³

et al. 2018

Preprint

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The Atg8/LC3/GABARAP protein family has been implicated in membrane remodeling events on the growing autophagosome. In particular, each of these proteins can form a protein-lipid conjugate that has been shown in vitro to drive liposome aggregation and in some cases membrane fusion. Furthermore, yeast Atg8 has been described as a curvature sensing protein, through its natural capacity to concentrate on highly curved membranes. A key advance with yeast Atg8, was the introduction of Giant Unilamellar Vesicles (GUVs) as an in vitro support that could allow membrane deformation and tethering to be observed by simple microscopy. Further, micromanipulation of an individual GUV could be used to create local areas of curvature to follow Atg8 partitioning. Here, we use a recently developed method to decorate GUVs with the mammalian Atg8 protein GABARAPL1 and establish the generality of the observations made on yeast Atg8. Then we apply double micromanipulation, the capture and positioning of two independently prepared GUVs, to test elements of the mechanism, speed and reversibility of mammalian Atg8 protein-mediated tethering. We find that the membranes adhere through GABARAPL1/GABARAPL1 homotypic trans-interactions. On a single membrane with two regions with significantly different curvatures we observed that the regions of higher curvature can be enriched up to 10 times in GABARAPL1 compared to the planar regions. This approach has the potential to allow the formation and study of specific topographically-controlled interfaces involving Atg8-proteins and their targets on apposing membranes.

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Section: Resultsmentioning

confidence: 99%

GABARAP Like-1 enrichment on membranes: Direct observation of trans-homo-oligomerization between membranes and curvature-dependent partitioning into membrane tubules

Motta¹,

Nguyen

Gardavot³

et al. 2018

Preprint

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“…This protein uses amphipathic helices at the tip of long molecular strings to sense high curvature on incoming vesicles before the engagement of soluble NSF attachment protein receptors (SNAREs), thereby increasing the fidelity of vesicle targeting. Other examples are the highly curved membrane sensing by the autophagosome-specific adaptor barkor (also known as Atg14L) that mediates the subsequent recruitment of class III phosphatidylinositol 3-kinase during autophagosome biogenesis (Fan et al, 2011), and the synergy between cargo recruitment by the autophagy receptor Atg19 and membrane bending of Atg8-coated membranes during autophagophore wrapping around the cargo (Sawa-Makarska et al, 2014).…”

Section: Membrane Targeting and Tetheringmentioning

confidence: 99%

Membrane curvature at a glance

McMahon

Boucrot

2015

Journal of Cell Science

621

589

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Membrane curvature is an important parameter in defining the morphology of cells, organelles and local membrane subdomains. Transport intermediates have simpler shapes, being either spheres or tubules. The generation and maintenance of curvature is of central importance for maintaining trafficking and cellular functions. It is possible that local shapes in complex membranes could help to define local subregions. In this Cell Science at a Glance article and accompanying poster, we summarize how generating, sensing and maintaining high local membrane curvature is an active process that is mediated and controlled by specialized proteins using general mechanisms: (i) changes in lipid composition and asymmetry, (ii) partitioning of shaped transmembrane domains of integral membrane proteins or protein or domain crowding, (iii) reversible insertion of hydrophobic protein motifs, (iv) nanoscopic scaffolding by oligomerized hydrophilic protein domains and, finally, (v) macroscopic scaffolding by the cytoskeleton with forces generated by polymerization and by molecular motors. We also summarize some of the discoveries about the functions of membrane curvature, where in addition to providing cell or organelle shape, local curvature can affect processes like membrane scission and fusion as well as protein concentration and enzyme activation on membranes.

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“…A recent study found that the Cvt vesicle cargo prApe1 facilitates the interaction of the cargo receptor Atg19 with Atg8 in the membrane (Sawa-Makarska et al, 2014). Atg19 contains multiple Atg8-binding motifs in its C-terminus, whereas its paralog Atg34 contains only one Atg8-binding motif.…”

Section: Membrane Modeling In Selective Autophagymentioning

confidence: 99%

Membrane dynamics in autophagosome biogenesis

Carlsson

Simonsen

2015

Journal of Cell Science

186

169

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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).

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Cargo binding to Atg19 unmasks additional Atg8 binding sites to mediate membrane–cargo apposition during selective autophagy

Cited by 102 publications

References 37 publications

GABARAP Like-1 enrichment on membranes: Direct observation of trans-homo-oligomerization between membranes and curvature-dependent partitioning into membrane tubules

GABARAP Like-1 enrichment on membranes: Direct observation of trans-homo-oligomerization between membranes and curvature-dependent partitioning into membrane tubules

Membrane curvature at a glance

Membrane dynamics in autophagosome biogenesis

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