A Pan1/End3/Sla1 complex links Arp2/3-mediated actin assembly to sites of clathrin-mediated endocytosis

Sun, Yidi; Leong, Nicole T; Wong, T. E.; Drubin, David G.

doi:10.1091/mbc.e15-04-0252

Cited by 67 publications

(87 citation statements)

References 43 publications

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“…Furthermore, myo5-TH1Δ in myo3Δ cells exhibited the frequent appearance of internal comet-like tails of Abp1-RFP that move throughout the cells. These structures resemble the structures that occur when endocytic coat proteins Pan1 and End3 are depleted (Sun et al, 2015), although this study provides evidence of this phenotype associated with a WASP/Myosin complex mutation. This phenotype also occurs in myo5Δ myo3Δ cells which also have no functional TH1 domains.…”

Section: Discussionmentioning

confidence: 53%

An Engineered Minimal WASP-Myosin Fusion Protein Reveals Essential Functions for Endocytosis

et al. 2015

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Summary Actin polymerization powers membrane deformation during many processes including clathrin-mediated endocytosis (CME). During CME in yeast, actin polymerization is triggered and coordinated by a six-protein WASP/Myosin complex that includes WASP, class I myosins (Myo3 and Myo5), WIP (Vrp1), and two other proteins. We show that a single engineered protein can replace this entire complex while still supporting CME. This engineered protein reveals that the WASP/Myosin complex has four essential activities; (1) recruitment to endocytic sites, (2) anchorage to the plasma membrane, (3) Arp2/3 activation, and (4) transient actin filament binding by the motor domain. The requirement for both membrane and F-actin binding reveals that myosin-mediated coupling between actin filaments and the base of endocytic sites is essential for allowing actin polymerization to drive membrane invagination.

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Section: Discussionmentioning

confidence: 53%

An Engineered Minimal WASP-Myosin Fusion Protein Reveals Essential Functions for Endocytosis

et al. 2015

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“…S9B), it displayed a dramatic synthetic sick phenotype when combined with deletion of SLA1 , which is involved in cortical actin assembly and endocytic vesicle formation, which translates into an extended Sla1 patch lifetime, reflecting a defect in endocytosis (Fig. 5A) (28). Second, given a negative trigenic interaction with OAF1 , which encodes an oleate-activated transcription factor involved in peroxisome organization and biogenesis (29), we used fluorescence microscopy to explore peroxisome morphology.…”

Section: Trigenic Interactions Expand Functional Connections Mapped Bmentioning

confidence: 99%

Systematic analysis of complex genetic interactions

Kuzmin

VanderSluis

Wang

et al. 2018

Science

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To systematically explore complex genetic interactions, we constructed ~200,000 yeast triple mutants and scored negative trigenic interactions. We selected double mutant query genes across a broad spectrum of biological processes, spanning a range of quantitative features of the global digenic interaction network and tested for a genetic interaction with a third mutation. Trigenic interactions often occurred among functionally related genes and essential genes were hubs on the trigenic network. Despite their functional enrichment, trigenic interactions tended to link genes in distant bioprocesses and display a weaker magnitude than digenic interactions. We estimate that the global trigenic interaction network is ~100-fold larger than the global digenic network, highlighting the potential for complex genetic interactions to impact the biology of inheritance, including the genotype to phenotype relationship.

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“…Among these proteins are the adaptor proteins such as Yap1801/1802 that link the clathrin coat to the phospholipid bilayer via the AP180 N‐terminal homology (ANTH) domains and adaptor proteins such as Ent1/2 and Sla2 that link actin to the phospholipid bilayer via epsin N‐terminal homology (ENTH) and ANTH domains, respectively . Additional EH domain‐containing coat proteins End3 and Pan1, together with Sla1, coordinate the timing of actin polymerization at endocytic sites by signaling a switch from patch establishment and endocytic receptor accumulation to active actin polymerization . Again, the EH domains of End3 and Pan1 are all adjacent to IDRs at either one or both sides of the domain, and the IDRs of Ent1, Pan1 and Sla2 are highly phosphorylated (Fig.…”

Section: Actin‐mediated Endocytosis and Endosomal Transportmentioning

confidence: 99%

Phospho‐regulation of intrinsically disordered proteins for actin assembly and endocytosis

et al. 2018

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Actin filament assembly contributes to the endocytic pathway pleiotropically, with active roles in clathrin-dependent and clathrin-independent endocytosis as well as subsequent endosomal trafficking. Endocytosis comprises a series of dynamic events, including the initiation of membrane curvature, bud invagination, vesicle abscission and subsequent vesicular transport. The ultimate success of endocytosis requires the coordinated activities of proteins that trigger actin polymerization, recruit actin-binding proteins (ABPs) and organize endocytic proteins (EPs) that promote membrane curvature through molecular crowding or scaffolding mechanisms. A particularly interesting phenomenon is that multiple EPs and ABPs contain a substantial percentage of intrinsically disordered regions (IDRs), which can contribute to protein coacervation and phase separation. In addition, intrinsically disordered proteins (IDPs) frequently contain sites for post-translational modifications (PTMs) such as phosphorylation, and these modifications exhibit a high preference for IDR residues [Groban ES et al. (2006) PLoS Comput Biol 2, e32]. PTMs are implicated in regulating protein function by modulating the protein conformation, protein-protein interactions and the transition between order and disorder states of IDPs. The molecular mechanisms by which IDRs of ABPs and EPs fine-tune actin assembly and endocytosis remain mostly unexplored and elusive. In this review, we analyze protein sequences of budding yeast EPs and ABPs, and discuss the potential underlying mechanisms for regulating endocytosis and actin assembly through the emerging concept of IDR-mediated protein multivalency, coacervation, and phase transition, with an emphasis on the phospho-regulation of IDRs. Finally, we summarize the current understanding of how these mechanisms coordinate actin cytoskeleton assembly and membrane curvature formation during endocytosis in budding yeast.

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A Pan1/End3/Sla1 complex links Arp2/3-mediated actin assembly to sites of clathrin-mediated endocytosis

Abstract: Eps15-related proteins couple the clathrin-mediated endocytic-site initiation and actin assembly phases and coordinate endocytic-site formation with cargo capture and actin assembly through their interaction with a CIN85-related protein.

Cited by 67 publications

References 43 publications

An Engineered Minimal WASP-Myosin Fusion Protein Reveals Essential Functions for Endocytosis

An Engineered Minimal WASP-Myosin Fusion Protein Reveals Essential Functions for Endocytosis

Systematic analysis of complex genetic interactions

Phospho‐regulation of intrinsically disordered proteins for actin assembly and endocytosis

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