The gut microbiome is a key partner of animals,influencing various aspects of their physiology and behaviors.Among the diverse behaviors regulated by the gut microbiome,locomotion is vital for survival and reproduction,although the underlying mechanisms remain unclear.Here,we reveal that the gut microbiome modulates the locomotor behavior of Drosophila larvae via a specific neuronal type in the brain.The crawling speed of germ-free(GF)larvae was significantly reduced compared to the conventionally reared larvae,while feeding and excretion behaviors were unaffected.Recolonization with Acetobacter and Lactobacillus can fully and partially rescue the locomotor defects in GF larvae,respectively,probably due to the highest abundance of Acetobacter as a symbiotic bacterium in the larval gut,followed by Lactobacillus.Moreover,the gut microbiome promoted larval locomotion,not by nutrition,but rather by enhancing the brain levels of tyrosine decarboxylase 2(Tdc2),which is an enzyme that synthesizes octopamine(OA).Overexpression of Tdc2 rescued locomotion ability in GF larvae.These findings together demonstrate that the gut microbiome specifically modulates larval locomotor behavior through the OA signaling pathway,revealing a new mechanism underlying larval locomotion regulated by the gut microbiome.
Juncheng HuRan BiYuxuan LuoKaihong WuShan JinZhihua LiuYicong JiaChuan-Xi Mao
Hematopoiesis is crucial for organismal health,and Drosophila serves as an effective genetic model due to conserved regulatory mechanisms with vertebrates.In larvae,hematopoiesis primarily occurs in the lymph gland,which contains distinct zones,including the cortical zone,intermediate zone,medullary zone,and posterior signaling center(PSC).Rab1 is vital for membrane trafficking and maintaining the localization of cell adhesion molecules,yet its role in hematopoietic homeostasis is not fully understood.This study investigates the effects of Rab1 dysfunction on β-integrin trafficking within circulating hemocytes and lymph gland cells.Rab1 impairment disrupts the endosomal trafficking of β-integrin,leading to its abnormal localization on cell membranes,which promotes lamellocyte differentiation and alters progenitor dynamics in circulating hemocytes and lymph glands,respectively.We also show that the mislocalization of β-integrin is dependent on the adhesion protein DE-cadherin.The reduction of β-integrin at cell boundaries in PSC cells leads to fewer PSC cells and lamellocyte differentiation.Furthermore,Rab1 regulates the trafficking of β-integrin via the Q-SNARE protein Syntaxin 17(Syx17).Our findings indicate that Rab1 and Syx17 regulate distinct trafficking pathways for β-integrin in different hematopoietic compartments and maintain hematopoietic homeostasis of Drosophila.
The host antimicrobial immune response relies on a complex interplay of molecular mechanisms to effectively combat microbial infections.Herein,we investigate the functional role of Cullin-3(Cul3),one critical constituent of Cullin-RING ubiquitin ligases,in the Drosophila melanogaster(fruit fly)antimicrobial immune defense.Weshow that silencing of Cul3 leads to a decreased induction of antimicrobial peptides and high mortality in adult flies after bacterial infection.Through biochemical approaches,we demonstrate that Cul3 predominantly relies on its BTB-binding domain and neddylation domain to physically associate with death-associated inhibitor of apoptosis 2(Diap2).Importantly,Cul3 ameliorates the Diap2-mediated ubiquitination of death-related ced-3/Nedd2-like caspase(Dredd),a process essential for robust immune deficiency signaling upon bacterial infection.Taken together,our findings highlight a previously unrecognized regulatory axis of Cul3/Diap2/Dredd in the fly antimicrobial immune defense,providing potential insights into therapeutic strategies for combating bacterial infections in humans.
Fanrui KongZixuan WangChuchu ZhangYihua XiaoMuhammad Abdul Rehman SaeedWeini LiAkira GotoQingshuang CaiShanming Ji
Animals exhibit complex responses to external and internal stimuli.The information is computed by interconnected neurons that express numerous ion channels,which modulate the neuronal membrane potential.How can neuronal activity orchestrate complex motor patterns or allow learning from previous experience?To answer such questions,we need the ability not only to record,but also to modulate neuronal activity in both space(e.g.,neuronal subsets)and time.
Neural damage or degeneration is at the crux of many diseases,and treatment of these diseases will require the development of therapeutics to enhance and guide neural regeneration.Both intrinsic and extrinsic factors dictate a neuron’s ability to regenerate,and the combination of these factors results in the great regenerative capacity of the peripheral nervous system(PNS)and the poor regenerative capacity of the central nervous system(CNS)following injury.At the core of a neuron’s function is its ability to relay electrochemical signals,and a neuron’s excitability is a key factor in its ability to regenerate.Recent works have focused on the changes in neuronal electrophysiological properties,firing patterns,and ion flux after injury,which differentially activate signaling pathways at the core of regeneration.The role of glia in neuron regeneration has long been studied.
Jackson PowellTobias SteinschadenRose HorowitzYuanquan Song
