Continuous endosomes form functional subdomains and orchestrate rapid membrane trafficking in trypanosomes.

Endocytosis is a common process observed in most eukaryotic cells, although its complexity varies among different organisms. In Trypanosoma brucei, the endocytic machinery is under special selective pressure because rapid membrane recycling is essential for immune evasion. This unicellular parasite effectively removes host antibodies from its cell surface through hydrodynamic drag and fast endocytic internalization. The entire process of membrane recycling occurs exclusively through the flagellar pocket, an extracellular organelle situated at the posterior pole of the spindle-shaped cell. The high-speed dynamics of membrane flux in trypanosomes do not seem compatible with the conventional concept of distinct compartments for early endosomes (EE), late endosomes (LE), and recycling endosomes (RE). To investigate the underlying structural basis for the remarkably fast membrane traffic in trypanosomes, we employed advanced techniques in light and electron microscopy to examine the three-dimensional architecture of the endosomal system. Our findings reveal that the endosomal system in trypanosomes exhibits a remarkably intricate structure. Instead of being compartmentalized, it constitutes a continuous membrane system, with specific functions of the endosome segregated into membrane subdomains enriched with classical markers for EE, LE, and RE. These membrane subdomains can partly overlap or are interspersed with areas that are negative for endosomal markers. This continuous endosome allows fast membrane flux by facilitated diffusion that is not slowed by multiple fission and fusion events.

Sustainability in Membrane Technology: Membrane Recycling and Fabrication Using Recycled Waste.

Membrane technology has shown a promising role in combating water scarcity, a globally faced challenge. However, the disposal of end-of-life membrane modules is problematic as the current practices include incineration and landfills as their final fate. In addition, the increase in population and lifestyle advancement have significantly enhanced waste generation, thus overwhelming landfills and exacerbating environmental repercussions and resource scarcity. These practices are neither economically nor environmentally sustainable. Recycling membranes and utilizing recycled material for their manufacturing is seen as a potential approach to address the aforementioned challenges. Depending on physiochemical conditions, the end-of-life membrane could be reutilized for similar, upgraded, and downgraded operations, thus extending the membrane lifespan while mitigating the environmental impact that occurred due to their disposal and new membrane preparation for similar purposes. Likewise, using recycled waste such as polystyrene, polyethylene terephthalate, polyvinyl chloride, tire rubber, keratin, and cellulose and their derivates for fabricating the membranes can significantly enhance environmental sustainability. This study advocates for and supports the integration of sustainability concepts into membrane technology by presenting the research carried out in this area and rigorously assessing the achieved progress. The membranes' recycling and their fabrication utilizing recycled waste materials are of special interest in this work. Furthermore, this study offers guidance for future research endeavors aimed at promoting environmental sustainability.

Coronavirus M Protein Trafficking in Epithelial Cells Utilizes a Myosin Vb Splice Variant and Rab10.

The membrane (M) glycoprotein of coronaviruses (CoVs) serves as the nidus for virion assembly. Using a yeast two-hybrid screen, we identified the interaction of the cytosolic tail of Murine Hepatitis Virus (MHV-CoV) M protein with Myosin Vb (MYO5B), specifically with the alternative splice variant of cellular MYO5B including exon D (MYO5B+D), which mediates interaction with Rab10. When co-expressed in human lung epithelial A549 and canine kidney epithelial MDCK cells, MYO5B+D co-localized with the MHV-CoV M protein, as well as with the M proteins from Porcine Epidemic Diarrhea Virus (PEDV-CoV), Middle East Respiratory Syndrome (MERS-CoV) and Severe Acute Respiratory Syndrome 2 (SARS-CoV-2). Co-expressed M proteins and MYO5B+D co-localized with endogenous Rab10 and Rab11a. We identified point mutations in MHV-CoV M that blocked the interaction with MYO5B+D in yeast 2-hybrid assays. One of these point mutations (E121K) was previously shown to block MHV-CoV virion assembly and its interaction with MYO5B+D. The E to K mutation at homologous positions in PEDV-CoV, MERS-CoV and SARS-CoV-2 M proteins also blocked colocalization with MYO5B+D. The knockdown of Rab10 blocked the co-localization of M proteins with MYO5B+D and was rescued by re-expression of CFP-Rab10. Our results suggest that CoV M proteins traffic through Rab10-containing systems, in association with MYO5B+D.

Membrane Life Cycle Management: An Exciting Opportunity for Advancing the Sustainability Features of Membrane Separations.

Membrane science and technology is growing rapidly worldwide and continues to play an increasingly important role in diverse fields by offering high separation efficiency with low energy consumption. Membranes have also shown great promise for "green" separation. A majority of the investigations in the field are devoted to the membrane fabrication and modification with the ultimate goals of enhancing the properties and separation performance of membranes. However, less attention has been paid to membrane life cycle management, particularly at the end of service. This is becoming very important, especially taking into account the trends toward sustainable development and carbon neutrality. On the contrary, this can be a great opportunity considering the large variety of membrane processes, especially in terms of the size and capacity of plants in operation. This work aims to highlight the prominent aspects that govern membrane life cycle management with special attention to life cycle assessment (LCA). While fabrication, application, and recycling are the three key aspects of LCA, we focus here on membrane (module) recycling at the end of life by elucidating the relevant aspects, potential criteria, and strategies that effectively contribute to the achievement of green development and sustainability goals.

The fates of internalized NaV1.7 channels in sensory neurons: Retrograde cotransport with other ion channels, axon-specific recycling, and degradation.

Neuronal function relies on the maintenance of appropriate levels of various ion channels at the cell membrane, which is accomplished by balancing secretory, degradative, and recycling pathways. Neuronal function further depends on membrane specialization through polarized distribution of specific proteins to distinct neuronal compartments such as axons. Voltage-gated sodium channel NaV1.7, a threshold channel for firing action potentials in nociceptors, plays a major role in human pain, and its abundance in the plasma membrane is tightly regulated. We have recently characterized the anterograde axonal trafficking of NaV1.7 channels in Rab6A-positive vesicles, but the fate of internalized channels is not known. Membrane proteins that have undergone endocytosis can be directed into multiple pathways including those for degradation, recycling to the membrane, and transcytosis. Here, we demonstrate NaV1.7 endocytosis and dynein-dependent retrograde trafficking in Rab7-containing late endosomes together with other axonal membrane proteins using real-time imaging of live neurons. We show that some internalized NaV1.7 channels are delivered to lysosomes within the cell body, and that there is no evidence for NaV1.7 transcytosis. In addition, we show that NaV1.7 is recycled specifically to the axonal membrane as opposed to the soma membrane, suggesting a novel mechanism for the development of neuronal polarity. Together, these results shed light on the mechanisms by which neurons maintain excitable membranes and may inform efforts to target ion channel trafficking for the treatment of disorders of excitability.

Thin Film Composite Polyamide Reverse Osmosis Membrane Technology towards a Circular Economy.

It is estimated that Reverse Osmosis (RO) desalination will produce, by 2025, more than 2,000,000 end-of-life membranes annually worldwide. This review examines the implementation of circular economy principles in RO technology through a comprehensive analysis of the RO membrane life cycle (manufacturing, usage, and end-of-life management). Future RO design should incorporate a biobased composition (biopolymers, recycled materials, and green solvents), improve the durability of the membranes (fouling and chlorine resistance), and facilitate the recyclability of the modules. Moreover, proper membrane maintenance at the usage phase, attained through the implementation of feed pre-treatment, early fouling detection, and membrane cleaning methods can help extend the service time of RO elements. Currently, end-of-life membranes are dumped in landfills, which is contrary to the waste hierarchy. This review analyses up to now developed alternative valorisation routes of end-of-life RO membranes, including reuse, direct and indirect recycling, and energy recovery, placing a special focus on emerging indirect recycling strategies. Lastly, Life Cycle Assessment is presented as a holistic methodology to evaluate the environmental and economic burdens of membrane recycling strategies. According to the European Commission's objectives set through the Green Deal, future perspectives indicate that end-of-life membrane valorisation strategies will keep gaining increasing interest in the upcoming years.

Validation of Recycled Nanofiltration and Anion-Exchange Membranes for the Treatment of Urban Wastewater for Crop Irrigation.

One of the alternative sources to tackle the problem of water shortage is the use of reclaimed water from wastewater treatment plants for irrigation purposes. However, when the wastewater has a high conductivity value, it becomes unusable for crop irrigation and needs a more specific treatment. In this work, recycled nanofiltration (rNF) membranes and anion-exchange membranes (rAEMs) obtained from end-of-life RO membranes were validated to evaluate their application capability in saline wastewater treatment. The use of recycled membranes may represent an advantage due to their lower cost and reduced environmental impact associated with their production, which integrates membrane-based technology into a circular economy model. Both recycled membranes were tested in crossflow filtration and electrodialysis (ED) systems. The results of the rNF membrane showed a high selective rejection of divalent ions (SO42− (>96%) and Ca2+ and Mg2+ (>93%)). In the case of the ED process, the comparison between rAEMs and commercial membranes showed an appropriate demineralization rate without compromising the power consumption. Finally, the quality of both system effluents was suitable for irrigation, which was compared to the WHO guideline and validated by the 7-week lettuce crop study.

Dictyostelium discoideum cells retain nutrients when the cells are about to outgrow their food source.

Dictyostelium discoideum is a unicellular eukaryote that eats bacteria, and eventually outgrows the bacteria. D. discoideum cells accumulate extracellular polyphosphate (polyP), and the polyP concentration increases as the local cell density increases. At high cell densities, the correspondingly high extracellular polyP concentrations allow cells to sense that they are about to outgrow their food supply and starve, causing the D. discoideum cells to inhibit their proliferation. In this report, we show that high extracellular polyP inhibits exocytosis of undigested or partially digested nutrients. PolyP decreases plasma membrane recycling and apparent cell membrane fluidity, and this requires the G protein-coupled polyP receptor GrlD, the polyphosphate kinase Ppk1 and the inositol hexakisphosphate kinase I6kA. PolyP alters protein contents in detergent-insoluble crude cytoskeletons, but does not significantly affect random cell motility, cell speed or F-actin levels. Together, these data suggest that D. discoideum cells use polyP as a signal to sense their local cell density and reduce cell membrane fluidity and membrane recycling, perhaps as a mechanism to retain ingested food when the cells are about to starve. This article has an associated First Person interview with the first author of the paper.

Nitrate Removal by Donnan Dialysis and Anion-Exchange Membrane Bioreactor Using Upcycled End-of-Life Reverse Osmosis Membranes.

This work explores the application of Reverse Osmosis (RO) upcycled membranes, as Anion Exchange Membranes (AEMs) in Donnan Dialysis (DD) and related processes, such as the Ion Exchange Membrane Bioreactor (IEMB), for the removal of nitrate from contaminated water, to meet drinking water standards. Such upcycled membranes might be manufactured at a lower price than commercial AEMs, while their utilization reinforces the commitment to a circular economy transition. In an effort to gain a better understanding of such AEMs, confocal µ-Raman spectroscopy was employed, to assess the distribution of the ion-exchange sites through the thickness of the prepared membranes, and 2D fluorescence spectroscopy, to evaluate alterations in the membranes caused by fouling and chemical cleaning The best performing membrane reached a 56% average nitrate removal within 24 h in the DD and IEMB systems, with the latter furthermore allowing for simultaneous elimination of the pollutant by biological denitrification, thus avoiding its discharge into the environment. Overall, this work validates the technical feasibility of using RO upcycled AEMs in DD and IEMB processes for nitrate removal. This membrane recycling concept might also find applications for the removal and/or recovery of other target negatively charged species.

To the Surface and Back: Exo- and Endocytic Pathways in Trypanosoma brucei.

Trypanosoma brucei is one of only a few unicellular pathogens that thrives extracellularly in the vertebrate host. Consequently, the cell surface plays a critical role in both immune recognition and immune evasion. The variant surface glycoprotein (VSG) coats the entire surface of the parasite and acts as a flexible shield to protect invariant proteins against immune recognition. Antigenic variation of the VSG coat is the major virulence mechanism of trypanosomes. In addition, incessant motility of the parasite contributes to its immune evasion, as the resulting fluid flow on the cell surface drags immunocomplexes toward the flagellar pocket, where they are internalized. The flagellar pocket is the sole site of endo- and exocytosis in this organism. After internalization, VSG is rapidly recycled back to the surface, whereas host antibodies are thought to be transported to the lysosome for degradation. For this essential step to work, effective machineries for both sorting and recycling of VSGs must have evolved in trypanosomes. Our understanding of the mechanisms behind VSG recycling and VSG secretion, is by far not complete. This review provides an overview of the trypanosome secretory and endosomal pathways. Longstanding questions are pinpointed that, with the advent of novel technologies, might be answered in the near future.

Electrospun Nanostructured Membrane Engineering Using Reverse Osmosis Recycled Modules: Membrane Distillation Application.

As a consequence of the increase in reverse osmosis (RO) desalination plants, the number of discarded RO modules for 2020 was estimated to be 14.8 million annually. Currently, these discarded modules are disposed of in nearby landfills generating high volumes of waste. In order to extend their useful life, in this research study, we propose recycling and reusing the internal components of the discarded RO modules, membranes and spacers, in membrane engineering for membrane distillation (MD) technology. After passive cleaning with a sodium hypochlorite aqueous solution, these recycled components were reused as support for polyvinylidene fluoride nanofibrous membranes prepared by electrospinning technique. The prepared membranes were characterized by different techniques and, finally, tested in desalination of high saline solutions (brines) by direct contact membrane distillation (DCMD). The effect of the electrospinning time, which is the same as the thickness of the nanofibrous layer, was studied in order to optimize the permeate flux together with the salt rejection factor and to obtain robust membranes with stable DCMD desalination performance. When the recycled RO membrane or the permeate spacer were used as supports with 60 min electrospinning time, good permeate fluxes were achieved, 43.2 and 18.1 kg m-2 h-1, respectively; with very high salt rejection factors, greater than 99.99%. These results are reasonably competitive compared to other supported and unsupported MD nanofibrous membranes. In contrast, when using the feed spacer as support, inhomogeneous structures were observed on the electrospun nanofibrous layer due to the special characteristics of this spacer resulting in low salt rejection factors and mechanical properties of the electrospun nanofibrous membrane.

JIP4 is recruited by the phosphoinositide-binding protein Phafin2 to promote recycling tubules on macropinosomes.

Macropinocytosis allows cells to take up extracellular material in a non-selective manner into large vesicles called macropinosomes. After internalization, macropinosomes acquire phosphatidylinositol 3-phosphate (PtdIns3P) on their limiting membrane as they mature into endosomal-like vesicles. The molecular mechanisms that underlie recycling of membranes and transmembrane proteins from these macropinosomes still need to be defined. Here, we report that JIP4 (officially known as SPAG9), a protein previously described to bind to microtubule motors, is recruited to tubulating subdomains on macropinosomes by the PtdIns3P-binding protein Phafin2 (officially known as PLEKHF2). These JIP4-positive tubulating subdomains on macropinosomes contain F-actin, the retromer recycling complex and the retromer cargo VAMP3. Disruption of the JIP4-Phafin2 interaction, deletion of Phafin2 or inhibition of PtdIns3P production by VPS34 impairs JIP4 recruitment to macropinosomes. Whereas knockout of JIP4 suppresses tubulation, its overexpression enhances tubulation from macropinosomes. JIP4-knockout cells display increased retention of macropinocytic cargo in both early and late macropinosomes. Collectively, these data identify JIP4 and Phafin2 as components of a tubular recycling pathway that operates from macropinosomes. This article has an associated First Person interview with the first author of the paper.

Arabidopsis phosphatidylinositol 4-phosphate 5-kinase genes PIP5K7, PIP5K8, and PIP5K9 are redundantly involved in root growth adaptation to osmotic stress.

Phosphatidylinositol 4-phosphate 5-kinase (PIP5K) produces phosphatidylinositol (4,5)-bisphosphate (PtdIns(4,5)P2 ), a signaling phospholipid critical for various cellular processes in eukaryotes. The Arabidopsis thaliana genome encodes 11 PIP5K genes. Of these, three type B PIP5K genes, PIP5K7, PIP5K8, and PIP5K9, constitute a subgroup highly conserved in land plants, suggesting that they retain a critical function shared by land plants. In this study, we comprehensively investigated the biological functions of the PIP5K7-9 subgroup genes. Reporter gene analyses revealed their preferential expression in meristematic and vascular tissues. Their YFP-fusion proteins localized primarily to the plasma membrane in root meristem epidermal cells. We selected a mutant line that was considered to be null for each gene. Under normal growth conditions, neither single mutants nor multiple mutants of any combination exhibited noticeable phenotypic changes. However, stress conditions with mannitol or NaCl suppressed main root growth and reduced proximal root meristem size to a greater extent in the pip5k7pip5k8pip5k9 triple mutant than in the wild type. In root meristem epidermal cells of the triple mutant, where plasma membrane localization of the PtdIns(4,5)P2 marker P24Y is impaired to a large extent, brefeldin A body formation is retarded compared with the wild type under hyperosmotic stress. These results indicate that PIP5K7, PIP5K8, and PIP5K9 are not required under normal growth conditions, but are redundantly involved in root growth adaptation to hyperosmotic conditions, possibly through the PtdIns(4,5)P2 function promoting plasma membrane recycling in root meristem cells.

Nitrate-Selective Anion Exchange Membranes Prepared using Discarded Reverse Osmosis Membranes as Support.

The present work shows a methodology for the preparation of membranes with a high affinity for nitrates. For this purpose, a polymeric mixture containing an anion exchange resin was extended on a recycled pressure filtration membrane used as mechanical support. Different ion exchange resins were tested. The influence in ion fractionation of (i) the type of ion exchange resin, (ii) the use of a recycled membrane as support and (iii) the operating current density during the separation process were studied. Results revealed that the employed anion exchange resin could tune up the transport numbers of the anions in the membrane and enhance the transport of nitrates over sulfates. The use of the recycled filtration membrane as support further increased the transport of nitrates in detriment of sulfates in nitrate-selective membranes. Moreover, it considerably improved the mechanical stability of the membranes. Lowering the operational current density also boosted ion fractionation. In addition, the use of recycled membranes as support in membrane preparation is presented as an alternative management route of discarded reverse osmosis membranes, coupling with the challenging management of waste generated by the desalination industry. These membranes could be used for nitrate recovery from wastewater or for nitrate separation from groundwater.

Macropinocytosis-mediated membrane recycling drives neural crest migration by delivering F-actin to the lamellipodium.

Individual cell migration requires front-to-back polarity manifested by lamellipodial extension. At present, it remains debated whether and how membrane motility mediates this cell morphological change. To gain insights into these processes, we perform live imaging and molecular perturbation of migrating chick neural crest cells in vivo. Our results reveal an endocytic loop formed by circular membrane flow and anterograde movement of lipid vesicles, resulting in cell polarization and locomotion. Rather than clathrin-mediated endocytosis, macropinosomes encapsulate F-actin in the cell body, forming vesicles that translocate via microtubules to deliver actin to the anterior. In addition to previously proposed local conversion of actin monomers to polymers, we demonstrate a surprising role for shuttling of F-actin across cells for lamellipodial expansion. Thus, the membrane and cytoskeleton act in concert in distinct subcellular compartments to drive forward cell migration.

Chemically Functionalized Water-Soluble Single-Walled Carbon Nanotubes Obstruct Vesicular/Plasmalemmal Recycling in Astrocytes Down-Stream of Calcium Ions.

We used single-walled carbon nanotubes chemically functionalized with polyethylene glycol (SWCNT-PEG) to assess the effects of this nanomaterial on astrocytic endocytosis and exocytosis. We observed that the SWCNT-PEG do not affect the adenosine triphosphate (ATP)-evoked Ca2+ elevations in astrocytes but significantly reduce the Ca2+-dependent glutamate release. There was a significant decrease in the endocytic load of the recycling dye during constitutive and ATP-evoked recycling. Furthermore, SWCNT-PEG hampered ATP-evoked exocytotic release of the loaded recycling dye. Thus, by functionally obstructing evoked vesicular recycling, SWCNT-PEG reduced glutamate release from astrocytes via regulated exocytosis. These effects implicate SWCNT-PEG as a modulator of Ca2+-dependent exocytosis in astrocytes downstream of Ca2+, likely at the level of vesicle fusion with/pinching off the plasma membrane.

SNX27 regulates DRA activity and mediates its direct recycling by PDZ-interaction in early endosomes at the apical pole of Caco2 cells.

DRA (downregulated in adenoma, SLC26A3) and NHE3 (Na+/H+ exchanger 3, SLC9A3) together mediate intestinal electroneutral NaCl absorption. Both transporters contain PDZ (postsynaptic density 95, disc large, zonula occludens 1) binding motifs and interact with PDZ adaptor proteins regulating their activity and recycling. SNX27 (sorting nexin 27) contains a PDZ domain and is involved in the recycling of cargo proteins including NHE3. The interaction of SNX27 with DRA and its potential role for the activity and recycling of DRA have been evaluated in this study. SNX27 specifically interacts with DRA via its PDZ domain. The knockdown (KD) of SNX27 reduced DRA activity by 50% but was not accompanied by a decrease of DRA surface expression. This indicates that DRA is trafficked to specific functional domains in the plasma membrane in which DRA is particularly active. Consistently, the disruption of lipid raft integrity by methyl-ß-cyclodextrin has an inhibitory effect on DRA activity that was strongly reduced after SNX27 KD. In differentiated intestinal Caco2 cells, superresolution microscopy and a novel quantitative axial approach revealed that DRA and SNX27 colocalize in rab5-positive early endosomes at the apical pole. SNX27 regulates the activity of DRA in the apical plasma membrane through binding with its PDZ domain. This interaction occurs in rab5-positive early endosomes at the apical pole of differentiated intestinal Caco2 cells. SNX27 is involved in the direct recycling of DRA to the plasma membrane where it is inserted into lipid rafts facilitating increased activity.NEW & NOTEWORTHY SNX27 has a PDZ domain and is involved in the regulation and recycling of transmembrane proteins. The role of SNX27 on the activity and recycling of the intestinal Cl-/HCO3- exchanger DRA has not yet been studied. This study shows that SNX27 directly interacts with DRA in early endosomes at the apical pole of intestinal Caco2 cells and mediates its direct recycling to facilitate high activity in lipid rafts in the apical plasma membrane.

Influence of acid/base activation treatment in the performance of recycled electromembrane for fresh water production by electrodialysis.

In this study, an activation treatment for recycled anion exchange membranes is proposed. Following the circular economy approach, these membranes were prepared by using end-of-life reverse osmosis membranes as mechanical support. The end-of-life membrane was previously used and discarded by desalination plants after overcoming its lifespan. The activation treatment was based on the subsequent immersion of the membranes in diluted acid and alkali solutions. This treatment promoted the complete dissociation of the functional groups in the membrane, making them more reactive to the counter ions. The effects of acid and alkali concentrations and exposition times on the electrochemical properties were studied and the best combination was selected. In such a way, a decrease of 37% in membrane electrical resistance was achieved. The performance of activated and non-activated membranes in brackish water desalination by electrodialysis was compared. The results showed that the proposed activation treatment increased the flux of fresh water more than four-fold (from 1.2 to 4.9 L h-1·m-2), with a considerable reduction of energy consumption (from 5.2 to 3.0 kWh·m-3) and a great improvement in current efficiency (from 38% to 71%). In conclusion, this work shows a simple and low cost methodology for the improvement of the electrochemical properties of recycled electromembranes and thus, their performance in electrodialysis.

Bench and pilot scale performance assessment of recycled membrane converted from old nanofiltration membranes.

Recycling of end-of-life polyamide-based thin film composite (TFC) membranes is gaining interest in academic and industrial contexts. The effects of chlorine exposure on the performance of polyamide membranes result in an increase in membrane permeability, whereas the solute rejection decreases. Therefore, the controlled chemical conversion of old reverse osmosis (RO) membranes has been reported by some previous papers. The objectives of this study were to assess recycling of old nanofiltration (NF) membrane, to assess the performance of the recycled membranes for a river water treatment application, and to conduct preliminary cost evaluations. Recycling technique consisted of exposing the membrane to a sodium hypochlorite solution in order to remove its polyamide layer and conversion to a low-pressure membrane. The work conducted bench scale and long-time pilot tests, and the recycled membranes showed a low fouling tendency. The difference between some results in bench- and pilot scale underscores the importance of evaluating design parameters using pilot scale units. Based on the cost analysis, the total cost of chemical recycling end-of-line NF membranes for a river water treatment is approximately 1.1% of the cost of using a new UF membrane. There is a great potential in using recycled membranes for rivers water treatments.

CD13 regulation of membrane recycling: implications for cancer dissemination.

Membrane recycling is critical to numerous cell functions and its dysregulation contributes to cancer and metastasis. We established that activation of the transmembrane molecule aminopeptidase N (ANPEP, also known as CD13) tethers the IQ motif containing, guanosine triphosphate hydrolase activating protein 1 (IQGAP1) scaffolding protein at the plasma membrane, thus stimulating the recycling regulator ADP-ribosylation factor 6 (ARF6) to ensure proper recycling of ß1-integrin and other membrane components impacting cell attachment.