Abstracts Category : Other

Newly Discovered Muscarinic Acetylcholine Receptors in thePrimary Cilia

by Hannah C Saternos

Primary endothelial cilia are mechanosensoryorganelles that are projected into the lumen of blood vessels.Defects in cilia assembly or function can lead to multiple humanpathologies, collectively known as ciliopathies, includingpolycystic kidney disease and associated hypertension.Acetylcholine, a neurotransmitter, is implicated in essentialhypertension in humans and animal models. It has been demonstratedthat vascular endothelia require primary cilia to sense andtransmit external mechanical stimuli into internal biochemicalreactions. One of these reactions includes the biosynthesis andrelease of nitric oxide, which is one of the most potent endogenousvasodilators. Though both primary cilia and muscarinicacetylcholine receptors play important roles in vascularhypertension, their relationship has never been explored. Todetermine the roles of the cholinergic system and mechanosensorycilia, we studied the effects of acetylcholine on ciliary lengthand function in wild-type (WT) and mechano-insensitive cilia mutantendothelial cells (Pkd1-/- and Tg737orpk/orpk). AChMR activationsignificantly increases cilia length in endothelial cells treatedwith Ach (1.490.006 vs 3.460.02 for wild-type and 0.960.003 vs.3.460.08 for Pkd1-/-) compared to control non-treated cells. Weshow for the first time that not only mouse vascular endotheliaexhibit muscarinic receptor-type 1, 3 and 5 (AChM1-, 3-, and 5R)co-localization to primary cilia, but also kidney epithelia exhibitmuscarinic receptor-type 1 and 3 colocalization to primary cilia.Data from AChMRs localization and expression experiments clearlypoints towards a role of AChMRs in cell division regulation andtowards their involvement in the pathogenesis in PKD.Advisors/Committee Members: AbouAlaiwi, Wissam (Committee Chair).