https://ogma.newcastle.edu.au/vital/access/ /manager/Index en-au 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:32970 in vitro, ex vivo, and in vivo. Results The number of CD151⁺ ASM cells is significantly greater in patients with moderate asthma compared with those in healthy nonasthmatic subjects. From loss- and gain-of-function studies, we reveal that CD151 is required for and enhances G protein-coupled receptor (GPCR)-induced peak intracellular calcium release, the primary determinant of excitation-contraction coupling. We show that the localization of CD151 can also be perinuclear/cytoplasmic and offer an explanation for a novel functional role for CD151 in supporting protein kinase C (PKC) translocation to the cell membrane in GPCR-mediated ASM contraction at this site. Importantly, CD151^-/- mice are refractory to airway hyperreactivity in response to allergen challenge. Conclusions We identify a role for CD151 in human ASM contraction. We implicate CD151 as a determinant of AHR in vivo, likely through regulation of GPCR-induced calcium and PKC signaling. These observations have significant implications in understanding the mechanism for AHR and the efficacy of new and emerging therapeutics.]]> Wed 17 Nov 2021 16:31:54 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:4527 Wed 11 Apr 2018 10:09:59 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:7003 Sat 24 Mar 2018 08:37:49 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:19252 Sat 24 Mar 2018 07:54:55 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:23404 IIbß₃, irreversible platelet aggregation and thrombus stabilisation. Tetraspanin superfamily member CD151 associates with integrin a_IIbß₃ and plays critical roles in regulation of thrombus growth and stability in vivo. The possible functional relationship between P2Y₁₂ and CD151 in a molecular cluster in platelets may affect thrombus formation. Hence our aim was to investigate the physical and functional requirements for this association in platelets. Our investigations reveal a specific and constitutive association between CD151 and P2Y₁₂ receptor in human platelets shown by immunoprecipitation/western blot studies and by flow cytometry. Specifically, the prominent association involves CD151 with P2Y₁₂ oligomers, and to a lesser extent P2Y₁₂ monomers. This association is not altered by platelet aggregation induced by different agonists. There is also a distinct complex of tetraspanin CD151 with ADP purinergic receptor P2Y₁₂ but not P2Y₁. P2Y₁₂ oligomer interaction with CD151 is selective as compared to other tetraspanins. To investigate the functional relationship between these receptors in platelets we used wild-type or CD151 knockout (KO) mice treated with either PBS or 50 mg/kg clopidogrel. CD151 KO mice treated with clopidogrel exhibited synergy in delayed kinetics of clot retraction, in PAR-4 and collagen-mediated platelet aggregation, platelet spreading on fibrinogen and without restricting cAMP inhibition. Clopidogrel treated CD151 KO arterioles showed smaller and less stable thrombi with increased tendency to embolise ex vivo and in vivo. These studies demonstrate a complementary role between CD151 and P2Y₁₂ receptor in platelets in regulating thrombus growth and stability.]]> Sat 24 Mar 2018 07:13:56 AEDT ]]>