Aagab is required for zebrafish larval development by regulating neural activity

Clathrin-mediated endocytosis has been implicated in various physiological processes,including nutrient uptake,signal transduction,synaptic vesicle recycling,maintenance of cell polarity,and antigen presentation.Despite prior knowledge of its importance as a key regulator in promoting clathrin-mediated endocytosis,the physiological function of α-and γ-adaptin binding protein(aagab)remains elusive.In this study,we investigate the biological function of aagab during zebrafish development.We establish a loss-of-function mutant of aagab in zebrafish,revealing impaired swimming and early larval mortality.Given the high expression level of aagab in the brain,we probe into its physiological role in the nervous system.aagab mutants display subdued calcium responses and local field potential in the optic tectal neurons,aligning with reduced neurotransmitter release(e.g.,norepinephrine)in the tectal neuropil of aagab mutants.Overexpressing aagab mRNA or nervous stimulant treatment in mutants restores neurotransmitter release,calcium responses,swimming ability,and survival.Furthermore,our observations show delayed release of FM 1-43 in AAGAB knockdown differentiated neuroblastoma cells,pointing towards a probable link to defective clathrin-mediated synaptic vesicle recycling.In conclusion,our study underscores the significance of Aagab in neurobiology and suggests its potential impacts on neurological disorders.

Light amplified oxidative stress in tumor microenvironment by carbonized hemin nanoparticles for boosting photodynamic anticancer therapy

Photodynamic therapy(PDT),which utilizes light excite photosensitizers(PSs)to generate reactive oxygen species(ROS)and consequently ablate cancer cells or diseased tissue,has attracted a great deal of attention in the last decades due to its unique advantages.However,the advancement of PDT is restricted by the inherent characteristics of PS and tumor microenvironment(TME).It is urgent to explore high-performance PSs with TME regulation capability and subsequently improve the therapeutic outcomes.Herein,we reported a newly engineered PS of polymer encapsulated carbonized hemin nanoparticles(P-CHNPs)via a facile synthesis procedure for boosting photodynamic anticancer therapy.Solvothermal treatment of hemin enabled the synthesized P-CHNPs to enhance oxidative stress in TME,which could be further amplified under light irradiation.Excellent in vitro and in vivo PDT effects were achieved due to the improved ROS(hydroxyl radicals and singlet oxygen)generation efficiency,hypoxia relief,and glutathione depletion.Moreover,the superior in vitro and in vivo biocompatibility and boosted PDT effect make the P-CHNPs a potential therapeutic agent for future translational research.

prpf4 is essential for cell survival and posterior lateral line primordium migration in zebrafish

Prpf4 （pre-mRNA processing factor 4）, a key component of spliceosome, plays critical roles in pre-mRNA splicing and its mutations result in retinitis pigmentosa due to photoreceptor defects. In this study, we characterized a zebrafish prpf4t243 mutant harboring a Tol2 transposon-based gene trap cassette in the third intron of the prpf4 gene. Cells in the brain and spinal cord gradually undergo p53-dependent apoptosis after 28 hpf in prpf4t243 mutants, suggesting that a widespread function of prpf4 in neural cell survival. In addition, prpf4 is essential for survival of posterior lateral line primordial （pLLP） cells, prpf4 deficiency perturbs Fgf, Wnt/β-catenin and chemokine signaling pathways and impairs pLLP migration. RNA-Seq analysis suggests that prpf4 deficiency may impair spliceosome assembly, leading to compensatory upregulation of core spliceosomal genes and alteration of pre-mRNA splicing. Taken together, our studies uncover an essential role of prpf4 in pre-mRNA splicing, cell survival and pLLP migration.