Biology subjects

Mei, F.

Publications and source records attributed to Mei, F..

6 recordsLinked to original sources

bioRxiv2026

Phagocytic activity of perivascular cell promotes CNS injury pathology

Injury, stroke, and neurological diseases cause persistent accumulation of cellular debris that deteriorates lesion microenvironment and impedes central nervous system (CNS) repair. Debris clearance in the injured CNS has long been attributed primarily to microglia and infiltrating macrophages. Here, we identify perivascular cells as previously unrecognized phagocytes that expand after injury and exhibit robust phagocytic activity. Perivascular cell phagocytosis is conserved across multiple mouse models of CNS injury and human stroke lesions. These cells exhibit key hallmarks of phagocytosis, including LC3-associated phagocytosis for efficient lysosomal degradation. Mechanistically, phosphatidylserine serves as the eat-me signal and Axl mediates myelin debris uptake. Myelin phagocytosis drives perivascular cell proliferation, fibrosis and lesion progression. Genetic deletion of Axl in perivascular cells or pharmacological inhibition with the FDA-approved Axl inhibitor Gilteritinib reduces pathology and improves functional recovery after spinal cord injury. Together, these findings establish Axl-dependent perivascular cell phagocytosis as a therapeutic target for CNS repair.

neuroscience↗

bioRxiv2025

A SUMO-interacting motif in the guanine nucleotide exchange factor EPAC1 is required for subcellular targeting and function

Exchange protein directly activated by cAMP (EPAC1), a multifunctional intracellular cAMP receptor, dynamically localizes to various cellular loci, engaging with diverse molecular partners to maintain cellular homeostasis. The study investigates the role of the SUMO interacting motif (SIM) in the subcellular targeting and cellular functions of EPAC1. It reveals that the SIM is a critical structural element for EPAC1s association with RanBP2/Nup358, a nucleoporin of the cytoplasmic filament component of the nuclear pore complex (NPC). Mutational disruption of EPAC1 SIM interferes with EPAC1s ability to activate its canonical effectors, small GTPases, Rap1 and Rap2, and non-canonical functions, such as the formation of nuclear condensates and cellular SUMOylation. Because SIM is also directly involved in cAMP binding, RanBP2s association with EPAC1 with the SIM attenuates EPAC1s cAMP binding affinity to generate an EPAC1 signaling microdomain with reduced cAMP sensitivity around the NPC. The coupling between EPAC1s scaffold association and cAMP binding enables EPAC1 to tune its sensitivity to stress stimuli spatially depending on the cellular locations. These findings provide novel structural insights into EPAC1 signaling, highlighting the importance of SIM in EPAC1s cellular functions and potential novel strategies for therapeutically targeting EPAC1.

cell biology↗

bioRxiv2024

Protein SUMOylation promotes cAMP-independent EPAC1 activation

Exchange protein directly activated by cAMP (EPAC1) mediates the intracellular functions of a critical stress-response second messenger, cAMP. Herein, we report that EPAC1 is a cellular substrate of protein SUMOylation, a prevalent stress-response posttranslational modification. Site-specific mapping of SUMOylation by mass spectrometer leads to identifying K561 as a primary SUMOylation site in EPAC1. Sequence and site-directed mutagenesis analyses reveal a functional SUMO-interacting motif required for cellular SUMOylation of EPAC1. SUMO modification of EPAC1 mediates its heat shock-induced Rap1/2 activation in a cAMP-independent manner. Structural modeling and molecular dynamics simulation studies demonstrate that SUMO substituent on K561 of EPAC1 promotes Rap1 interaction by increasing the buried surface area between the SUMOylated receptor and its effector. Our studies identify a functional SUMOylation site in EPAC1 and unveil a novel mechanism in which SUMOylation of EPAC1 leads to its autonomous activation. The findings of SUMOylation-mediated activation of EPAC1 not only provide new insights into our understanding of cellular regulation of EPAC1 but also will open up a new field of experimentation concerning the cross-talk between cAMP/EPAC1 signaling and protein SUMOylation, two major cellular stress response pathways, during cellular homeostasis.

cell biology↗

bioRxiv2020

Reappraisal of Spinach-based RNA Visualization in Plants

RNAs can be imaged in living cells using molecular beacons, RNA-binding labeled proteins and RNA aptamer-based approaches. However, Spinach RNA-mimicking GFP (RMG) has not been successfully used to monitor cellular RNAs in plants. In this study, we re-evaluated Spinach-based RNA visualization in different plants via transient, transgenic, and virus-based expression strategies. We found that like bacterial, yeast and human cellular tRNAs, plant tRNAs such as tRNALys (K) can protect and/or stabilize the spinach RNA aptamer interaction with the fluorophore DFHBI enabling detectable levels of green fluorescence to be emitted. The tRNALys-spinach-tRNALys (KSK), once delivered into "chloroplast-free" onion epidermal cells can emit strong green fluorescence in the presence of DFHBI. Transgenic or virus-based expression of monomer KSK, in either stably transformed or virus-infected Nicotinana benthamiana plants, failed to show RMG fluorescence. However, incorporating tandem repeats of KSK into recombinant viral RNAs, enabled qualitative and quantitative detection, both in vitro and ex vivo (ex planta), of KSK-specific green fluorescence, though RMG was less obvious in vivo (in planta). These findings demonstrate Spinach-based RNA visualization has the potential for ex vivo and in vivo monitoring RNAs in plant cells. One sentence summarySpinach-based RMG technology was reevaluated to have potential for ex vivo and in vivo monitoring RNAs in plant cells.

plant biology↗

bioRxiv2020

Assessment of whether published non-Cochrane systematic reviews of nursing follow the review protocols registered in the International Prospective Register of Systematic Reviews (PROSPERO): A comparative study

Purpose We compare published non-Cochrane reviews of nursing with their pre-registered protocols on PROSPERO to quantify the prevalence of differences and the extent to which the differences were explained.Methods We searched for protocols and their corresponding reviews in PROSPERO’s nursing group that were “completed and published” from inception to September 8th, 2019. Two authors independently identified differences and classified the difference as none, partial, or complete, and determined if the existed differences had been explained. Frequency (n), percentage (%), median, and inter-quartile ranges were used to analyze the extent of differences and explanations.Results We identified 22 pre-registered protocols and their reviews. All 22 pairs (100%) exhibited differences. Eighteen pairs (82%) showed differences in at least six methodological sections, while 21 pairs (95%) involved completed difference in at least one section. The median number of differences per review was 8.00 (upper quartile = 6.00, lower quartile = 9.75). The differences involved all 13 compared methodology-related sections. Only 5 (3%) of all differences were explained in the systematic reviews.Conclusions We observed widespread differences between non-Cochrane reviews of nursing and their protocols recorded in PROSPERO, with relatively few explanations for the changes. Measures including establishing a new item in the reporting guideline of systematic reviews to guide reporting and explaining the reasons for differences between protocols and systematic reviews or even requiring authors to do so at the Journal’s author guideline are recommended to improve transparency.View Full Text

scientific communication and education↗

bioRxiv2017

EPAC1 regulates endothelial Annexin A2 cell surface translocation and plasminogen activation

Annexins, a family of highly conserved calcium-and phospholipid-binding proteins, play important roles in a wide range of physiological functions. Among the twelve known annexins in human, Annexin A2 (AnxA2) is one of the most extensively studied and has been implicated in various human diseases. AnxA2 can exist as a monomer or a heterotetrameric complex with S100A10 (P11) and plays a critical role in many cellular processes including exocytosis/endocytosis and membrane organization. At the endothelial cell surface, (AnxA2*P11)2 tetramer, acting as a coreceptor for plasminogen and tissue plasminogen activator (t-PA), accelerates t-PA dependent activation of the fibrinolytic protease, plasmin, the enzyme responsible for thrombus dissolution and degradation of fibrin. This study shows that exchange proteins directly activated by cAMP isoform 1 (EPAC1) interacts with AnxA2 and regulates its biological functions by modulating its membrane translocation in endothelial cells. Using genetic and pharmacological approaches, it is demonstrated that EPAC1, acting through the PLC{varepsilon}-PKC pathway, inhibits AnxA2 surface translocation and plasminogen activation. These results suggest that EPAC1 plays a role in the regulation of fibrinolysis in endothelial cells and may represent a novel therapeutic target for disorders of fibrinolysis.

cell biology↗