Multiple primary cilia modulate the fluid transcytosis in choroid plexus epithelium.
Functional defects in cilia are associated with various human diseases including congenital hydrocephalus. Previous studies suggested that defects in cilia not only disrupt the flow of cerebrospinal fluid (CSF) generated by motile cilia in ependyma lining the brain ventricles, but also cause increased CSF production at the choroid plexus. However, the molecular mechanisms of CSF overproduction by ciliary dysfunction remain elusive. To dissect the molecular mechanisms, choroid plexus epithelial cells (CPECs) were isolated from porcine brain. These cells expressed clusters of primary cilia on the apical surface. Deciliation of CPECs elevated the intracellular cyclic AMP (cAMP) levels and stimulated basolateral-to-apical fluid transcytosis, without detrimental effects on other morphological and physiological features. The primary cilia possessed neuropeptide FF (NPFF) receptor 2. In deciliated cells, the responsiveness to NPFF was reduced at nanomolar concentrations. Furthermore, CPECs expressed NPFF precursor along with NPFFR2. An NPFFR antagonist, BIBP3226, increased the fluid transcytosis, suggesting the presence of autocrine NPFF signaling in CPECs for a tonic inhibition of fluid transcytosis. These results suggest that the clusters of primary cilia in CPECs act as a sensitive chemosensor to regulate CSF production.
Narita
Keishi
K
Department of Anatomy and Cell Biology, Interdisciplinary School of Medicine & Engineering, University of Yamanashi, 1110 Shimo-Kateau, Chuo, Yamanashi 409-3898, Japan.
Kawate
Toyoko
T
Kakinuma
Naoto
N
Takeda
Sen
S
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D019898:Autocrine Communication / Q000187:drug effects; D001483:Base Sequence; D018938:Caco-2 Cells; D002417:Cattle; D045744:Cell Line, Tumor; D002555:Cerebrospinal Fluid / Q000378:metabolism; D002831:Choroid Plexus / Q000166:cytology / Q000378:metabolism; D002923:Cilia / Q000378:metabolism* / Q000648:ultrastructure; D000242:Cyclic AMP / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D018013:Receptors, Neuropeptide / Q000378:metabolism; D013552:Swine
D014151:Anti-Anxiety Agents; C092926:BIBP 3226; D009842:Oligopeptides; D018013:Receptors, Neuropeptide; C083929:neuropeptide FF receptor; D001120:Arginine; C053651:phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide; D000242:Cyclic AMP