Targeting of the Arf-like GTPase Arl3p to the Golgi requires N-terminal acetylation and the membrane protein Sys1p

Behnia, Rudy; Panić, B.; Whyte, James R.C.; Munro, Sean

doi:10.1038/ncb1120

Cited by 242 publications

(254 citation statements)

References 47 publications

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“…The maturation process may effect this change in fusogenic potential by the recruitment or loss of specific components of the fusion machinery. Interestingly, other small four-transmembrane domain proteins, including Yip1p and Sys1p, are required for the recruitment of small GTPases to specific compartments (Yang et al, 1998;Behnia et al, 2004;Setty et al, 2004). Although we were unable to detect a physical association between the Vps55/68 complex and the endosomal Rab GTPase Vps21p, the presence of these proteins in the same phenotypic cluster suggests the Vps55/68 complex may interact transiently with Vps21p to fulfill a specific step in endosome maturation.…”

Section: The Vps55/68 Complex Is Required For Two Transport Steps Outcontrasting

confidence: 38%

Global Analysis of Yeast Endosomal Transport Identifies the Vps55/68 Sorting Complex

Schluter

Lam

Brumm

et al. 2008

MBoC

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Endosomal transport is critical for cellular processes ranging from receptor down-regulation and retroviral budding to the immune response. A full understanding of endosome sorting requires a comprehensive picture of the multiprotein complexes that orchestrate vesicle formation and fusion. Here, we use unsupervised, large-scale phenotypic analysis and a novel computational approach for the global identification of endosomal transport factors. This technique effectively identifies components of known and novel protein assemblies. We report the characterization of a previously undescribed endosome sorting complex that contains two well-conserved proteins with four predicted membrane-spanning domains. Vps55p and Vps68p form a complex that acts with or downstream of ESCRT function to regulate endosomal trafficking. Loss of Vps68p disrupts recycling to the TGN as well as onward trafficking to the vacuole without preventing the formation of lumenal vesicles within the MVB. Our results suggest the Vps55/68 complex mediates a novel, conserved step in the endosomal maturation process. INTRODUCTIONEndosomal protein sorting is a highly conserved cellular process that is required for receptor down-regulation, viral replication, and development (Katzmann et al., 2002;Morita and Sundquist, 2004). Much progress has been made in recent years in identifying distinct multiprotein complexes that regulate the fusion of primary endocytic vesicles, the maturation of an early endosome into a multivesicular body (MVB), and the recycling of proteins and lipids to other organelles (Gruenberg and Stenmark, 2004;Bonifacino and Rojas, 2006). The ESCRT-I, -II, and -III complexes (endosomal-sorting complex required for transport), which act in sequence to regulate the formation of internal vesicles at the MVB, play a central role in endosome biogenesis (Katzmann et al., 2002;Hurley and Emr, 2006). Other transport complexes regulate the targeting and fusion of endosomes or endosome-derived vesicles with other organelles (Bowers and Stevens, 2005;Bonifacino and Rojas, 2006).Many components of the endosomal-sorting machinery were first identified in yeast genetic screens for mutants that are defective in protein transport to the yeast vacuole, which requires functional endosomal sorting and recycling (Bowers and Stevens, 2005). Most of these components have a conserved role in endosome biogenesis in higher cells. Mammalian homologues have been identified for most if not all yeast ESCRT subunits (von Schwedler et al., 2003;Hurley and Emr, 2006), and at least some of the machinery that regulates recycling from the MVB is also well conserved. For example, the five-subunit retromer complex that mediates endosome-to-trans-Golgi network (TGN) transport in yeast is associated with tubular regions of the endosome in mammalian cells and mediates retrograde transport (Arighi et al., 2004;Seaman, 2004). In the past 20 years, classical genetic screens have identified more than 50 vacuole protein-sorting (VPS) genes (Bowers and Stevens, 2005). Surprisingly, ...

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Section: The Vps55/68 Complex Is Required For Two Transport Steps Outcontrasting

confidence: 38%

Global Analysis of Yeast Endosomal Transport Identifies the Vps55/68 Sorting Complex

Schluter

Lam

Brumm

et al. 2008

MBoC

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“…10 While the functional implications of this modification are not fully understood, a number of roles have been observed including enhancing protein-protein [11][12][13] and protein-membrane interactions 14,15 both of which are relevant to AS. Acetylation removes the N-terminal charge, making this region of the protein more hydrophobic.…”

Section: Resultsmentioning

confidence: 99%

N‐terminal acetylation is critical for forming α‐helical oligomer of α‐synuclein

2012

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The aggregation of the protein a-synuclein (AS) is critical to the pathogenesis of Parkinson's disease. Although generally described as an unstructured monomer, recent evidence suggests that the native form of AS may be an a-helical tetramer which resists aggregation. Here, we show that N-terminal acetylation in combination with a mild purification protocol results in an oligomeric form of AS with partial a-helical structure. N-terminal acetylation of AS could have important implications for both the native and pathological structures and functions of AS. Through our demonstration of a recombinant expression system, our results represent an important step toward biochemical and biophysical characterization of this potentially important form of AS.

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“…This altered complex still displays 60 -80% of the wild type NatA activity but appears to be lethal within few days after birth. Although NAA is associated to specific roles for several protein groups such as cytoskeleton protein binding (30 -32) or protein targeting to a given compartment (33)(34)(35), its intrinsic function has remained elusive for the large majority of the proteins. Nevertheless, it was suggested that NAA is an important factor influencing protein half-life either globally or in some protein groups (4, 36 -38).…”

mentioning

confidence: 99%

Comparative Large Scale Characterization of Plant versus Mammal Proteins Reveals Similar and Idiosyncratic N-α-Acetylation Features

Bienvenut

Sumpton

Martinez

et al. 2012

Molecular & Cellular Proteomics

159

193

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Targeting of the Arf-like GTPase Arl3p to the Golgi requires N-terminal acetylation and the membrane protein Sys1p

Cited by 242 publications

References 47 publications

Global Analysis of Yeast Endosomal Transport Identifies the Vps55/68 Sorting Complex

Global Analysis of Yeast Endosomal Transport Identifies the Vps55/68 Sorting Complex

N‐terminal acetylation is critical for forming α‐helical oligomer of α‐synuclein

Comparative Large Scale Characterization of Plant versus Mammal Proteins Reveals Similar and Idiosyncratic N-α-Acetylation Features

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