Membrane dynamics and fusion at late endosomes and vacuoles – Rab regulation, multisubunit tethering complexes and SNAREs

Epp, Nadine; Rethmeier, Ralf; Krämer, Lukas; Ungermann, Christian

doi:10.1016/j.ejcb.2011.04.007

Cited by 64 publications

(63 citation statements)

References 65 publications

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“…When early endosomes mature, three membrane-active complexes act on endosomes likely in a coordinated manner: (i) receptors and other membrane proteins that are destined for downregulation will be sorted into intraluminal vesicles via the ESCRT complexes (Henne et al , 2011 ); (ii) recycling of cargo receptors that deliver hydrolases to the vacuole occurs via the retromer complex (Bonifacino and Hurley , 2008 ); and (iii) finally, fusion of mature late endosomes occurs via Rab7, its HOPS effector complex, and the endolysosomal SNAREs (Figure 2) (Epp et al , 2011 ). It is expected that the first two machineries act in para llel and could separate the cargo into microdomains on membranes via their respective binding affinities.…”

Section: Even Though the Exact Organization Of Such Zonesmentioning

confidence: 99%

Cellular microcompartments constitute general suborganellar functional units in cells

Holthuis

Ungermann

2013

Biological Chemistry

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All cells are compartmentalized to facilitate enzymatic reactions or cellular dynamics. In eukaryotic cells, organelles differ in their protein/lipid repertoire, luminal ion composition, pH, and redox status. In addition, organelles contain specialized subcompartments even within the same membrane or within its lumen. Moreover, the bacterial plasma membrane reveals a remarkable degree of organization, which is recapitulated in eukaryotic cells and often linked to cell signaling. Finally, protein-based compartments are also known in the bacterial and eukaryotic cytosol. As the organizing principle of such cellular subcompartments is likely similar, previous definitions like rafts, microdomains, and all kinds of ' -somes ' fall short as a general denominator to describe such suborganellar structures. Within this review, we will introduce the term cellular microcompartment as a general suborganellar functional unit and discuss its relevance to understand subcellular organization and function.

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Section: Even Though the Exact Organization Of Such Zonesmentioning

confidence: 99%

Cellular microcompartments constitute general suborganellar functional units in cells

Holthuis

Ungermann

2013

Biological Chemistry

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“…On the basis of its homology to HOPS, the CORVET complex has been postulated to act as a tethering complex as well (2,4,12,14). However, it has remained challenging to find solid evidence supporting such a function.…”

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confidence: 99%

“…They receive their membrane and protein load via endocytosis from the plasma membrane and from Golgi-derived vesicles that deliver, among others, vacuolar hydrolases. Within the yeast endocytic pathway, we distinguish early endosomes and late endosomes (also called prevacuolar compartment or multivesicular body) (1)(2)(3)(4). Many lines of evidence suggest that early endosomes mature into late endosomes, which is accompanied by recycling of cargo receptors back to the Golgi and plasma membrane mediated by the retromer and Snx4/41/42 complexes (5-7).…”

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confidence: 99%

Functional Separation of Endosomal Fusion Factors and the Class C Core Vacuole/Endosome Tethering (CORVET) Complex in Endosome Biogenesis

Cabrera

Arlt

Epp

et al. 2013

Journal of Biological Chemistry

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Background:The interdependence of the endosomal fusion factors CORVET and Vac1 has not been addressed. Results: CORVET can be separated from other endocytic fusion factors on the basis of ultrastructure, localization, and trafficking. Conclusion: CORVET acts independently of the Vac1 tether and requires activated Rab5 homologs for localization. Significance: Our data reveal a unique role of CORVET in sorting of biosynthetic cargo to the vacuole.

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“…Regulation of membrane dynamics is crucial for normal cellular processes as well as the survival of tumor cells, and the process involves the activity of an array of intracellular proteins (Gerke & Moss, 1997;Borgonovo et al, 2002;Tekpli et al, 2011;Epp et al, 2011;Cheng & Lane, 2010;Saarikangas et al, 2010). When the integrity of the plasma membrane is compromised, intracellular proteins involved in membrane repair localize to the site of damage and in many cases are activated by the influx in Ca 2+ ions from the extracellular matrix (Draeger et al, 2011;Bischofberger et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Structure of a C-terminal AHNAK peptide in a 1:2:2 complex with S100A10 and an acetylated N-terminal peptide of annexin A2

Ozorowski

Milton

Luecke

2012

Acta Crystallogr D Biol Crystallogr

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AHNAK, a large 629 kDa protein, has been implicated in membrane repair, and the annexin A2–S100A10 heterotetramer [(p11)2(AnxA2)2)] has high affinity for several regions of its 1002‐amino‐acid C‐terminal domain. (p11)2(AnxA2)2 is often localized near the plasma membrane, and this C2‐symmetric platform is proposed to be involved in the bridging of membrane vesicles and trafficking of proteins to the plasma membrane. All three proteins co‐localize at the intracellular face of the plasma membrane in a Ca2+‐dependent manner. The binding of AHNAK to (p11)2(AnxA2)2 has been studied previously, and a minimal binding motif has been mapped to a 20‐amino‐acid peptide corresponding to residues 5654–5673 of the AHNAK C‐terminal domain. Here, the 2.5 Å resolution crystal structure of this 20‐amino‐acid peptide of AHNAK bound to the AnxA2–S100A10 heterotetramer (1:2:2 symmetry) is presented, which confirms the asymmetric arrangement first described by Rezvanpour and coworkers and explains why the binding motif has high affinity for (p11)2(AnxA2)2. Binding of AHNAK to the surface of (p11)2(AnxA2)2 is governed by several hydrophobic interactions between side chains of AHNAK and pockets on S100A10. The pockets are large enough to accommodate a variety of hydrophobic side chains, allowing the consensus sequence to be more general. Additionally, the various hydrogen bonds formed between the AHNAK peptide and (p11)2(AnxA2)2 most often involve backbone atoms of AHNAK; as a result, the side chains, particularly those that point away from S100A10/AnxA2 towards the solvent, are largely interchangeable. While the structure‐based consensus sequence allows interactions with various stretches of the AHNAK C‐terminal domain, comparison with other S100 structures reveals that the sequence has been optimized for binding to S100A10. This model adds new insight to the understanding of the specific interactions that occur in this membrane‐repair scaffold.

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Membrane dynamics and fusion at late endosomes and vacuoles – Rab regulation, multisubunit tethering complexes and SNAREs

Cited by 64 publications

References 65 publications

Cellular microcompartments constitute general suborganellar functional units in cells

Cellular microcompartments constitute general suborganellar functional units in cells

Functional Separation of Endosomal Fusion Factors and the Class C Core Vacuole/Endosome Tethering (CORVET) Complex in Endosome Biogenesis

Structure of a C-terminal AHNAK peptide in a 1:2:2 complex with S100A10 and an acetylated N-terminal peptide of annexin A2

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