Localization of transient receptor potential ion channels in primary and motile cilia of the female murine reproductive organs

Abstract

We have examined the subcellular localization of transient receptor potential (TRP) ion channels and the potential sensory role of cilia in murine female reproductive organs using confocal laser scanning microscopy analysis on ovary and oviduct tissue sections as well as on primary cultures of follicular granulosa cells. We show that the Ca2+ permeable cation channel, polycystin-2, as well as polycystin-1, a receptor that forms a functional protein complex with polycystin 2, distinctively localize to primary cilia emerging from granulosa cells of antral follicles in vivo and in vitro. Both polycystins are localized to motile oviduct cilia and this localization is greatly increased upon ovulatory gonadotropic stimulation. Further, the Ca2+ permeable cation channel, TRP vaniloid 4 (TRPV4), localizes to a sub-population of motile cilia on the epithelial cells of the ampulla and isthmus with high intensity in proximal invaginations of the epithelial folds. These observations are the first to demonstrate ciliary localization of TRP ion channels and their possible receptor function in the female reproductive organs. We suggest that polycystins 1 and 2 play an important role in granulosa cell differentiation and in development and maturation of ovarian follicles. In the oviduct both TRPV4 and polycystins could be important in relaying physiochemical changes in the oviduct upon ovulation.

The Hedgehog signaling pathway in ovarian teratoma is stimulated by Sonic Hedgehog which induces internalization of Patched

“…However, when prostate cancer cell lines were examined under different growth conditions, there was no evidence of cilia formation (46). The cilia were also normally detected in the ovary, more specifically in the granulosa cells of the pre-antral and antral follicles (47). When cultured, these cells exhibit cilia only after serum starvation and growth arrest, while normal interphase cells show a complex cytoskeletal network but no primary cilia (47).…”

Far from solved: A perspective on what we know about early mechanisms of left–right asymmetry

“…Cilia do indeed possess ion channels (Teilmann et al, 2005) and even neurotransmitter receptors (Brailov et al, 2000;Berbari et al, 2008), so perhaps gradients other than calcium (McGrath et al, 2003;Schneider et al, 2008) also function during ciliary flow at the node. The very early presence of the relevant ion transporter proteins does not rule out this model, because, like ciliary proteins themselves which can also be expressed long before ciliogenesis, they could be present but not functioning in LR asymmetry until cilia appear.…”

Role of Primary Cilia in the Pathogenesis of Polycystic Kidney Disease

“…Although the cilia membrane is contiguous with the plasma membrane, its composition is distinct, and protein entry into the ciliary membrane domain is tightly regulated. Several key signaling proteins have been localized to this organelle, including channels such as transient receptor potential vanilloid 4; the cystic kidney disease-associated proteins polycystin-1 and -2; and receptors for somatostatin (SSTR-3), serotonin (HT-6), angiopoietin (Tie-1 and Tie-2), hedgehog (smoothened), and PDGF (PDGFR␣) (32)(33)(34)(35)(36). Although the molecular mechanism that directs these proteins into the cilia is unknown, the current model predicts that they dock with the terminal plate and transition fibers and are loaded onto the transport machinery for delivery into the cilium.…”