Shear stress activates nociceptors to drive Drosophila mechanical nociception

TrpA1 is a shear stress mechanosensing channel regulating intestinal stem cell proliferation in Drosophila

“…AITC has been shown to activate Ca 2+ signals in enterochromaffin cells and stimulate serotonin release ( 57 ). As we have recently shown that mammalian TrpA1 behaves similarly to Drosophila TrpA1 by responding to shear stress ( 24 ), it will be of interest to determine whether enterochromaffin cells in mammals could sense shear stress through TrpA1 and, if so, whether shear stress sensing of enterochromaffin cells could play a role in gut growth and physiology.…”

“…For immunostaining studies, adult female flies were used at indicated age. The following fly strains were used in this study: w 1118 (gift from P. Emery), TrpA1-D-2A-Gal4 ( 21 ), esg-Gal4 (BL#84324), myo1A-Gal4 ( 32 ), UAS-GCaMP6s (BL#42746, BL#42749), TrpA1-C-2A-Gal4 ( 21 ), Pros-Gal4 (BL#84276), TK-2A-Gal4 (BL#84693), DH31-Gal4 (BL#51988), TrpA1-GFP ( 21 ), AstA-2A-Gal4 (BL#84593), AstC-2A-Gal4 (BL#84595), CCHA1-2A-Gal4 (BL#84361), CCHA2-2A-Gal4 (BL#84602), CG30340-2A-Gal4 (BL#84611), DH31-2A-Gal4 (BL#84623), MIP-2A-Gal4 (BL#84651), UAS-6XGFP (BL#52262), LexAop-6XmCherry (BL#52267), TrpA1-2A-Gal4 ( 21 ), TrpA1-2A-LexA ( 21 ), UAS-luciferase-RNAi (BL#31603), UAS-TrpA1-RNAi (BL#36780), TrpA1-KO ( 21 ), R61H07-Gal4 (BL#39282), UAS-TrpA1-A ( 21 ), UAS-TrpA1-D ( 21 ), UAS-TrpA1-D-E1017K ( 24 ), TrpA1-FLAG ( 21 ), Gr28b-LexA (lab stock), LexAOP-GCaMP6s (BL#44589), elav-Gal80 (lab stock), TrpA1-A-KI ( 21 ), TrpA1-D-KI ( 21 ), UAS-EGFP-RNAi (BL#41552), UAS-mCherry.NLS (BL#38425), and tubP-Gal80 ts (BL#7018).…”

“…While there is presumed mechanosensing processes, e.g., stretch and shear stress, caused by food particles and fluid passing through the intestinal lumen, the detailed mechanisms of mechanosensing in the gut epithelium and how that may regulate intestinal tissue growth are just beginning to be found (12)(13)(14)(15)(16)(17)(18)(19). Here, we show that a member of the Ca 2+ -permeable transient receptor potential (Trp) channels family, Drosophila TrpA1, a polymodal sensory ion channel that is known to be activated by heat and noxious chemicals and is involved in mechanical nociception (20)(21)(22)(23)(24)(25), mediates shear stress sensing of EEs to indirectly regulate ISC activity and intestine growth.…”

Ether phospholipids modulate somatosensory responses by tuning multiple receptor functions inDrosophila

“…We then used different GAL4 lines for AGPS knockdown to identify the mechanosensory neurons involved in the reduction in mechanical nociception. Several receptor genes have been reported as responsible for the von Frey filament responses, including PIEZO 32 , TRPA1-C/D 30, 33 , ppk 34 , and painless 35 . When AGPS RNAi was induced using PIEZO-GAL4 and TRPA1-CD GAL 4 , a significant decrease in the response to the von Frey filament (20.1 mN) was observed (p < 0.05 in Dunnett test) (Fig.…”

Mechanotransduction in the urothelium: ATP signalling and mechanoreceptors

“…TRPV4-KO mice displayed phenotypes resembling urinary incontinence; iii. Intravesical instillation with TRPV4-selective agonist induced bladder overactivity and increased maximal voiding pressure by 51% in mice [ 16 , 21 , 23 , 201 , 203 , 212 , 216 , [276] , [277] , [278] ] TRPA1 Cold (<17 °C) Alkaline pH Distension Fluid flow Human Mouse Rat Activation of TRPA1 enhanced the contraction in the urinary bladder strips, which was inhibited by blockade Intravesical administration of AI increased voiding frequency and reduced voided volume in conscious rats [ 239 , 245 , [279] , [280] , [281] , [282] ] TRPM7 Acidic pH (≤6) Fluid flow Stretch Hypotonicity Human Mouse TRPM7-mediated Mg 2+ concentration dependent currents were observed in cultured urothelial cells Voided volume was reduced in urothelial TRPM7-KO mice [ [255] , [256] , [257] , 283 ] Piezo1 Poking Stretch Hypotonicity Fluid flow Human Mouse Rat i. Stimulation of urothelial cells by mechanical stretch and hypotonic swelling induced Piezo1-mediated Ca 2+ influx and ATP release, which were attenuated by inhibitors and siRNA; ii. The simultaneous loss of Piezo1/2 had a significant effect on poking-induced Ca 2+ influx in umbrella cells and ATP release from the serosal surfaces of the urothelium i.…”