Biology subjects

Davey, M.

Publications and source records attributed to Davey, M..

At least 19 recordsLinked to original sources

bioRxiv2026

Parallel visual processing in the suprachiasmatic region of a diurnal mammal.

Light shapes mammalian physiology and behaviour through hypothalamic pathways, yet how these pathways process visual information in day-active species remains poorly understood. Based largely on work in nocturnal rodents, the suprachiasmatic nucleus (SCN) is classically viewed as a retinal target that encodes ambient illumination for circadian entrainment. We combine anatomical tracing, light-evoked c-Fos mapping and high-density silicon-probe electrophysiology to define visual processing in the suprachiasmatic region of the diurnal murid Rhabdomys pumilio. We find that retinal input and light-evoked activity extend beyond the SCN into rostral and lateral peri-SCN hypothalamus. Within the SCN, neurons encode irradiance with graded changes in maintained firing broadly similar to those observed in parallel recordings of nocturnal Mus domesticus. Across the wider suprachiasmatic region, Rhabdomys neurons show selectivity for more dynamic visual stimuli, including luminance transitions, contrast and temporal structure. Unsupervised clustering identifies five functionally distinct hypothalamic visual response classes with different anatomical distributions. These findings reveal an expanded hypothalamic visual network in a diurnal mammal, placing SCN irradiance coding within a broader system for processing dynamic visual features.

neuroscience↗

bioRxiv2026

Two intramolecular interfaces control the WDR44 conformational switch that regulates Rab11 binding

Rab GTPases coordinate distinct membrane trafficking pathways through interactions with specialized effector proteins. Rab11 is a central regulator of endocytic recycling and also drives preciliary trafficking to the centriole. Both pathways depend on the Rab11 effector WDR44, which promotes Rab11-dependent recycling but suppresses ciliogenesis in serum-grown cells. WDR44 engages Rab11 through an N-terminal Rab11-binding domain that is autoinhibited by an intramolecular interaction with the C-terminal WD40 domain, and pathogenic WD40-domain variants that cause ciliopathies relieve this inhibition. How the closed conformation is maintained, however, has not been defined. Here we combine structural modeling and mutational analysis with a bystander BRET assay that reports WDR44 recruitment to Rab11 compartments in living cells, and identify two N-terminal segments that engage distinct surfaces of the WD40 domain. The larger segment extends across the top face of the domain, where reported pathogenic variants cluster, while a second segment contacts the side. Disrupting either segment weakens the intramolecular interaction and promotes WDR44 recruitment to Rab11 compartments. Our work defines the contacts that maintain WDR44 in its closed conformation and provides a mechanism by which pathogenic mutations may alter WDR44 function.

cell biology↗

bioRxiv2026

The VPS9-family GEF VINE activates Ypt10 in a late endosomal Rab cascade

Rab GTPase cascades drive endosomal membrane maturation by sequentially activating and inactivating Rab proteins. These transitions in Rab signaling require the coordinated actions of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). The yeast VINE complex is an endosomal VPS9-family GEF that stimulates a GAP to inactivate the Rab5 homolog Vps21, suggesting a role for VINE in coordinating Rab transitions. Here we report that VINE acts through its catalytic GEF domain to promote signaling by the Rab5-related GTPase Ypt10 and establish a pool of Ypt10 at late endosomes. Ypt10 activation occurs downstream of Vps21 activity, placing Ypt10 within a late endosomal Rab cascade. Genome-wide protein proximity screens revealed a VINE-dependent interaction between Ypt10 and the GEF Mon1-Ccz1. Our data suggest that VINE and Ypt10 regulate late endosomal recruitment of Mon1-Ccz1 to enhance the activation of its substrate, the Rab7 homolog Ypt7. Together, these findings define a Vps21-VINE-Ypt10 regulatory module that adds a layer of control within the late endosomal Vps21-to-Ypt7 cascade and establish VINE as a dual Rab regulator. Through opposing activities on Vps21 and Ypt10, VINE may couple Rab5 inactivation to Mon1-Ccz1 recruitment to provide more precise control of degradative protein traffic to the vacuole. Significance statementFour Rab5-family GTPases direct protein sorting and membrane maturation in the yeast endolysosomal system, yet their individual functions, and the role of the little-studied Rab Ypt10, are unclear. Using genome-wide proximity screens, we find that the GEF complex VINE establishes a pool of Ypt10 at late endosomes downstream of Vps21, where Ypt10 recruits Mon1-Ccz1, the activator of the Rab7 homolog Ypt7. Because VINE also drives GAP-mediated suppression of Vps21, our results suggest it acts as a dual Rab regulator, coupling Vps21 inactivation to Ypt10 activation to fine-tune the endosomal Rab cascade.

cell biology↗

bioRxiv2026

Septins associate with AP-3 to support trafficking to the vacuole/lysosome in yeast

Adaptor protein complex 3 (AP-3) mediates clathrin-independent transport to lysosomes, yet accessory factors supporting this pathway remain incompletely defined. In Saccharomyces cerevisiae, the C-terminal intrinsically disordered regions (IDRs) of both AP-3 large subunits ({delta} and {beta}3) serve as platforms for association with accessory factors. Through proteomic analysis of proteins associated with these IDRs, we identify the septin cytoskeleton as a candidate AP-3-associated factor. Bimolecular fluorescence complementation (BiFC) reveals a hierarchical pattern of association: AP-3 shows preferential proximity to core septin subunits (Cdc10, Cdc3, Cdc12) over terminal subunits (Cdc11 and Shs1). These terminal subunits serve as alternative caps of septin octamers, generating structurally distinct assemblies. Significantly, dysfunction of Cdc11 but not Shs1 selectively impairs AP-3-dependent cargo sorting without affecting the parallel vacuolar protein sorting (VPS) pathway to the vacuole (lysosome in yeast), providing genetic evidence for a specific functional connection between Cdc11-containing septin assemblies and AP-3-mediated transport.

cell biology↗

bioRxiv2026

The Rab GEF VINE couples phosphatase recruitment to GAP-mediated Rab5 inactivation

Rab5-family GTPases cycle between active and inactive forms to regulate endosomal membrane identity and protein trafficking. VPS9-family guanine nucleotide exchange factors (GEFs) promote Rab activation at endosomes, whereas GTPase-activating proteins (GAPs) oppose Rab signaling. Here, we identify an unexpected role for the yeast VPS9-family GEF complex VINE in promoting the inactivation of the Rab5 homolog Vps21. Through genome-wide proximity screening, predictive modeling, targeted mutagenesis and in vivo assays, we show that VINE recruits the protein phosphatase Glc7 through the ankyrin repeat-containing domain of its GEF subunit Vrl1. Our results suggest this directs the dephosphorylation of Kxd1, a subunit of the GAP adaptor BLOC-1, which in turn enhances its interaction with the Vps21-specific GAP Msb3 and accelerates GAP-mediated Vps21 inactivation. Thus, VINE is a VPS9-family GEF complex that selectively limits endosomal Rab signaling. These findings reveal a novel mechanism integrating positive and negative Rab regulation, providing insight into how Rab5 signaling is fine-tuned during endosomal trafficking and maturation.

cell biology↗

bioRxiv2025

A shared binding interface controls Vps13 organelle-specific targeting independently of its vacuolar protein sorting function

Yeast vacuolar protein sorting 13 (Vps13) is a bridge-like transporter that directs lipid flow between membranes at organelle contact sites. Vps13 targeting relies on organelle-specific adaptors containing proline-X-proline (PxP) motifs, which compete for binding to the Vps13 adaptor-binding (VAB) domain. Though a VAB-PxP interface has been identified for the mitochondrial adaptor Mcp1, whether other adaptors use identical binding mechanisms is unknown. Moreover, not every Vps13 function is connected to a known PxP adaptor, suggesting other adaptors may exist. Here, we validate the significance of the shared VAB-PxP interface by showing that mutations within this region inhibit both adaptor binding and Vps13 membrane targeting in vivo. Using predictive modeling, we demonstrate that while adaptors share a common Vps13-binding interface, slight differences between these interfaces may contribute to preferential binding and adaptor competition. Notably, we find that the VPS pathway functions independently of the PxP motif binding site, and extensive scanning mutagenesis did not reveal a dedicated VPS-specific adaptor interface. Our results indicate the VPS pathway likely employs a non-PxP adaptor mechanism, yet the structural integrity of the VAB domain remains essential for proper pathway function. Significance statementO_LIAdaptor-mediated recruitment of yeast Vps13 to organelles requires a consensus PxP motif. It is unclear if all adaptors bind Vps13 in a similar manner and if all Vps13 functions are dependent on adaptors that contain this motif. C_LIO_LIWe show that Vps13 binds the core PxP motifs from known adaptors through a shared interface, yet this interface is dispensable for Vps13s role in the vacuole protein sorting pathway. C_LIO_LIOur work suggests that Vps13 engages in a wider range of targeting mechanisms than was previously recognized, and that the Vps13 adaptor-binding domain must have a function beyond targeting this consensus motif. C_LI

cell biology↗

bioRxiv2025

The molecular mechanism of lipid uptake by membrane-anchored bridge-like lipid transfer proteins.

Lipid transport by bridge-like lipid transfer proteins (BLTPs) is emerging as a key process in lipid and cellular metabolism in both physiological and pathological conditions. However, the precise mechanism of lipid transport by BLTPs has remained elusive. Here, we use extensive all-atom molecular dynamics simulations to characterize the precise mechanism of lipid transfer into the BLTP hydrophobic cavity from donor membranes. For multiple BLTPs, we observe the ability to extract and solubilize lipids without lipid selectivity, and we identify membrane destabilization as a critical parameter to achieve effective lipid desorption. We rationally design a mutant BLTP with altered ability to destabilize lipid bilayers, and we show that this abolishes lipid desorption in silico and protein function in vivo. Taken together, our data provide an atomic-level description of the mechanism of lipid transport by BLTPs, ultimately suggesting alternative strategies to interfere with their activity.

biophysics↗

bioRxiv2025

TMEM170 family proteins are lipid scramblases that physically associate with bridge lipid transporters BLTP1/Csf1

Bulk lipid transport between organelles has been proposed to involve the partnership between bridge lipid transport proteins and membrane-embedded lipid scramblases. However, for almost all BLTPs, such physical association has not been fully described, and, in most cases, the identity of the scramblases is unknown. Here, we identify TMEM170 family proteins as endoplasmic reticulum lipid scramblases that physically interact with BLTP1/Csf1 proteins. This finding opens new avenues to understand the complex mechanism involved in lipid transport at membrane contact sites.

cell biology↗

bioRxiv2025

Hoi1 targets the yeast BLTP2 protein to ER-PM contact sites to regulate lipid homeostasis

Membrane contact sites between organelles are important for maintaining cellular lipid homeostasis. Members of the recently identified family of bridge-like lipid transfer proteins (BLTPs) span opposing membranes at these contact sites to enable the rapid transfer of bulk lipids between organelles. While the VPS13 and ATG2 family members use organelle-specific adaptors for membrane targeting, the mechanisms that regulate other bridge-like transporters remain unknown. Here, we identify the conserved protein Ybl086c, which we name Hoi1 (Hob interactor 1), as an adaptor that targets the yeast BLTP2-like proteins Fmp27/Hob1 and Hob2 to ER-PM contact sites. Two separate Hoi1 domains interface with alpha-helical projections that decorate the central hydrophobic channel on Fmp27, and loss of these interactions disrupts cellular sterol homeostasis. The mutant phenotypes of BLTP2 and HOI1 orthologs indicate these proteins act in a shared pathway in worms and flies. Together, this suggests that Hoi1-mediated recruitment of BLTP2-like proteins represents an evolutionarily conserved mechanism for regulating lipid transport at membrane contact sites.

cell biology↗

bioRxiv2024

An acylated N-terminus and a conserved loop regulate the activity of the ABHD17 de-acylase

The dynamic addition and removal of long chain fatty acids modulates protein function and localization. The alpha/beta hydrolase domain-containing (ABHD) 17 enzymes remove acyl chains from membrane localized proteins such as the oncoprotein NRas, but how the ABHD17 proteins are regulated is unknown. Here, we used cell-based studies and molecular dynamics simulations to show that ABHD17 activity is controlled by two mobile elements - an S-acylated N-terminal helix and a loop - that flank the substrate-binding pocket. S-acylation at multiple sites buries the helix in the membrane, which allows hydrophobic residues in the loop to interact with the bilayer. This stabilizes the conformation of both helix and loop, alters the conformation of the binding pocket and optimally positions the enzyme for substrate engagement. S-acylation may be a general feature of acyl-protein thioesterases. By providing a mechanistic understanding of how the lipid modification of a lipid-removing enzyme promotes its enzymatic activity, this work contributes to our understanding of cellular S-acylation cycles.

cell biology↗

bioRxiv2024

Unveiling the Molecular Mechanisms of the Type-IX Secretion System's Response Regulator: Structural and Functional Insights

The Type-IX secretion system (T9SS) is a nanomachinery utilized by bacterial pathogens to facilitate infection. The system is regulated by a signaling cascade serving as its activation switch. A pivotal member in this cascade, the response regulator protein PorX, represents a promising drug target to prevent the secretion of virulence factors. Here, we provide a comprehensive characterization of PorX both in vitro and in vivo. First, our structural studies revealed PorX harbours a unique enzymatic effector domain, which, surprisingly, shares structural similarities with the alkaline phosphatase superfamily, involved in nucleotide and lipid signaling pathways. Importantly, such pathways have not been associated with the T9SS until now. Enzymatic characterization of PorXs effector domain revealed a zinc-dependent phosphodiesterase activity, with active site dimensions suitable to accommodate a large substrate. Unlike typical response regulators that dimerize via their receiver domain upon phosphorylation, we found that zinc can also induce conformational changes and promote PorXs dimerization via an unexpected interface. These findings suggest that PorX can serve as a cellular zinc sensor, broadening our understanding of its regulatory mechanisms. Despite the strict conservation of PorX in T9SS-utilizing bacteria, we demonstrate that PorX is essential for virulence factors secretion in Porphyromonas gingivalis and affects metabolic enzymes secretion in the non-pathogenic Flavobacterium johnsoniae, but not for the secretion of gliding adhesins. Overall, this study advances our structural and functional understanding of PorX, highlighting its potential as a druggable target for intervention strategies aimed at disrupting the T9SS and mitigating virulence in pathogenic species.

biochemistry↗

bioRxiv2024

Inhibition of SARS-CoV-2 infection by Porphyromonas gingivalis and the oral microbiome

The COVID-19 pandemic persists despite the availability of vaccines, and it is therefore crucial to develop new therapeutic and preventive approaches. In this study, we investigated the potential role of the oral microbiome in SARS-CoV-2 infection. Using an in vitro SARS-CoV-2 pseudovirus infection assay, we found a potent inhibitory effect exerted by Porphyromonas gingivalis on SARS-CoV-2 infection mediated by known P. gingivalis compounds such as phosphoglycerol dihydroceramide (PGDHC) and gingipains as well as by unknown bacterial factors. We found that the gingipain-mediated inhibition of infection is likely due to cytotoxicity, while PGDHC inhibited virus infection by an unknown mechanism. Unidentified factors present in P. gingivalis supernatant inhibited SARS-CoV-2 likely via the fusion step of the virus life cycle. We addressed the role of other oral bacteria and found certain periodontal pathogens capable of inhibiting SARS-CoV-2 pseudovirus infection by inducing cytotoxicity on target cells. In the human oral cavity, we observed the modulatory activity of oral microbial communities varied among individuals in that some saliva-based cultures were capable of inhibiting while others were enhancing infection. These findings contribute to our understanding of the complex relationship between the oral microbiome and viral infections, offering potential avenues for innovative therapeutic strategies in combating COVID-19.

microbiology↗

bioRxiv2024

N-terminal signals in the SNX-BAR paralogs Vps5 and Vin1 guide coat complex formation

Endosomal coat complexes assemble by incorporating membrane-binding subunits such as those of the sorting nexin (SNX) family. The S. cerevisiae SNX-BAR paralogs Vin1 and Vps5 are respective subunits of the endosomal VINE and retromer complexes that arose from a fungal whole genome duplication. Interactions mediated by the Vin1 and Vps5 BAR domains are required for protein complex assembly and membrane association. However, a degree of promiscuity is predicted for yeast BAR-BAR pairings, suggesting that another mechanism guides the formation of specific endosomal coat complexes. Previous work by our group and others has implicated the unstructured N-terminal domains of Vin1 and Vps5 in complex assembly. Here, we map N-terminal signals in both SNX-BAR paralogs that contribute to the formation and function of two distinct endosomal coats in vivo. Whereas Vin1 leverages a polybasic region and adjacent hydrophobic motif to bind Vrl1 and form VINE, the N-terminus of Vps5 interacts with the retromer subunit Vps29 at two separate sites. We show that one of these Vps5 motifs binds to a conserved hydrophobic pocket in Vps29 that is shared with other accessory proteins and targeted by a bacterial virulence factor in humans. Lastly, we examined the sole isoform of Vps5 from the milk yeast K. lactis and found that ancestral yeasts may have used a nested N-terminal signal to form both VINE and retromer. Our results suggest that the specific assembly of Vps5-family SNX-BAR coats depends on inputs from unique N-terminal sequence features in addition to BAR domain coupling, expanding our understanding of endosomal coat assembly mechanisms.

cell biology↗

bioRxiv2023

Elevation-dependent patterns of snow-gum dieback are moderated by trait differences between montane and subalpine forests.

Subalpine forests worldwide face the synergistic threats of global warming and increased biotic attack, and the collapse or transition of subalpine forests is predicted in south-eastern Australia under future climates. The recent widespread dieback of subalpine snow gum forests due to increased activity of a native wood-boring longicorn beetle suggests this process may already be underway. We investigated how variation in tree tissue traits and environmental conditions correlated with elevation-dependent spatial patterns of forest mortality. We hypothesised that increased vulnerability of subalpine snow gums to wood-borer-mediated dieback at intermediate elevations was associated with poorly-resolved differences in traits between montane (Eucalyptus pauciflora subsp. pauciflora) and subalpine (E. pauciflora subsp. niphophila) snow-gum subspecies. We first sought to characterise variation and elevation-dependent transitions in 20 structural and drought-related functional traits among 120 healthy trees distributed along a 1000m elevation transect which spanned the subspecies transition zone. Secondly, we surveyed 774 trees across 53 sites between 1280-1980m asl. to explore associations between borer-damage severity, elevation, subspecies, and a subset of traits that differed between subspecies. These snow-gum subspecies exhibited mean differences and/or divergent elevation responses in 25% of traits surveyed, indicating contrasting suites of traits between montane and subalpine subspecies. Increased borer-damage severity across the montane-to-subalpine subspecies transition was correlated with lower bark thickness, whereas reduced borer damage at the highest elevations was associated with greater precipitation and lower temperatures. Our results suggest that due to possessing distinct traits associated with increased borer susceptibility, subalpine snow-gum forests will be subject to increased risk of severe borer-mediated forest dieback under warmer and drier future climates. Identifying traits contributing to species distribution limits and biotic-agent vulnerability remains critical for predicting, monitoring, and possibly mitigating forest and vegetation declines under future climates.

ecology↗

bioRxiv2023

Genome-wide screen identifies new set of genes for improved heterologous laccase expression in Saccharomyces cerevisiae

The yeast Saccharomyces cerevisiae is widely used as a host cell for recombinant protein production due to its fast growth, cost-effective culturing, and ability to secrete large and complex proteins. However, one major drawback is the relatively low yield of produced proteins compared to other host systems. To address this issue, we developed an overlay assay to screen the yeast knockout collection and identify mutants that enhance recombinant protein production, specifically focusing on the secretion of the Trametes trogii fungal laccase enzyme. Gene ontology analysis of these mutants revealed an enrichment of processes including vacuolar targeting, vesicle trafficking, proteolysis, and glycolipid metabolism. We confirmed that a significant portion of these mutants also showed increased activity of the secreted laccase when grown in liquid culture. Notably, we found that the combination of deletions of OCA6, a tyrosine phosphatase, along with PMT1 or PMT2, two ER membrane protein-O-mannosyltransferases involved in ER quality control, and SKI3, a component of the SKI complex responsible for mRNA degradation, further increased secreted laccase activity. Conversely, we also identified over 200 gene deletions that resulted in decreased secreted laccase activity, including many genes that encode for mitochondrial proteins and components of the ER-associated degradation pathway. Intriguingly, the deletion of the ER DNAJ co-chaperone SCJ1 led to almost no secreted laccase activity. When we expressed SCJ1 from a low-copy plasmid, laccase secretion was restored. However, overexpression of Scj1p had a detrimental effect, indicating that precise dosing of key chaperone proteins is crucial for optimal recombinant protein expression. ImportanceOur study showcases a newly developed high throughput screening technique to identify yeast mutant strains that exhibit an enhanced capacity for recombinant protein production. Using a genome-wide approach, we show that vesicle trafficking plays a crucial role in protein production, as the genes associated with this process are notably enriched in our screen. Furthermore, we demonstrate that a specific set of gene deletions, which were not previously recognized for their impact on recombinant laccase production, can be effectively manipulated in combination to increase the production of heterologous proteins. This study offers potential strategies for enhancing the overall yield of recombinant proteins and provides new avenues for further research in optimizing protein production systems.

microbiology↗

bioRxiv2022

Overexpression of the WAPO-A1 gene increases the number of spikelets per spike in bread wheat

Two homoeologous QTLs for number of spikelets per spike (SPS) were mapped on chromosomes 7AL and 7BL using two wheat MAGIC populations. Sets of lines contrasting for the QTL on 7AL were developed which allowed for the validation and fine mapping of the 7AL QTL and for the identification of a previously described candidate gene, WHEAT ORTHOLOG OF APO1 (WAPO1). Using transgenic overexpression in both a low and a high SPS line, we provide a functional validation for the role of this gene in determining SPS also in hexaploid wheat. We show that the expression levels of this gene positively correlate with SPS in multiple MAGIC founder lines under field conditions as well as in transgenic lines grown in the greenhouse. This work highlights the potential use of WAPO1 in hexaploid wheat for further yield increases. The impact of WAPO1 and SPS on yield depends on other genetic and environmental factors, hence, will require a finely balanced expression level to avoid the development of detrimental pleiotropic phenotypes.

plant biology↗

bioRxiv2022

Real-time dynamic single-molecule protein sequencing on an integrated semiconductor device

Proteins are the main structural and functional components of cells, and their dynamic regulation and post-translational modifications (PTMs) underlie cellular phenotypes. Next-generation DNA sequencing technologies have revolutionized our understanding of heredity and gene regulation, but the complex and dynamic states of cells are not fully captured by the genome and transcriptome. Sensitive measurements of the proteome are needed to fully understand biological processes and changes to the proteome that occur in disease states. Studies of the proteome would benefit greatly from methods to directly sequence and digitally quantify proteins and detect PTMs with single-molecule sensitivity and precision. However current methods for studying the proteome lag behind DNA sequencing in throughput, sensitivity, and accessibility due to the complexity and dynamic range of the proteome, the chemical properties of proteins, and the inability to amplify proteins. Here, we demonstrate single-molecule protein sequencing on a compact benchtop instrument using a dynamic sequencing by stepwise degradation approach in which single surface-immobilized peptide molecules are probed in real-time by a mixture of dye-labeled N-terminal amino acid recognizers and simultaneously cleaved by aminopeptidases. By measuring fluorescence intensity, lifetime, and binding kinetics of recognizers on an integrated semiconductor chip we are able to annotate amino acids and identify the peptide sequence. We describe the expansion of the number of recognizable amino acids and demonstrate the kinetic principles that allow individual recognizers to identify multiple amino acids in a highly information-rich manner that is sensitive to adjacent residues. Furthermore, we demonstrate that our method is compatible with both synthetic and natural peptides, and capable of detecting single amino acid changes and PTMs. We anticipate that with further development our protein sequencing method will offer a sensitive, scalable, and accessible platform for studies of the proteome.

biophysics↗

bioRxiv2021

The VINE complex is a VPS9-domain GEF-containing SNX-BAR coat involved in endosomal sorting

Membrane trafficking pathways perform important roles in establishing and maintaining the endolysosomal network. Retrograde protein sorting from the endosome is promoted by conserved SNX-BAR-containing coat complexes including retromer which enrich cargo at tubular microdomains and generate transport carriers. In metazoans, retromer cooperates with VARP, a conserved VPS9-domain GEF, to direct an endosomal recycling pathway. The function of the yeast VARP homolog Vrl1 has been overlooked due an inactivating mutation in commonly studied strains. Here, we demonstrate that Vrl1 has features of a SNX-BAR coat protein and forms an obligate complex with Vin1, the paralog of the retromer SNX-BAR protein Vps5. Unique features in the Vin1 N-terminus allow Vrl1 to distinguish it from Vps5, thereby forming what we have named the VINE complex. VINE occupies endosomal tubules and promotes the delivery of a conserved mannose 6-phosphate receptor-like protein to the vacuolar membrane. In addition to sorting functions, membrane recruitment by Vin1 is essential for Vrl1 GEF activity, suggesting that VINE is a multifunctional coat complex that regulates trafficking and signaling events at the endosome.

cell biology↗