Research Article: Adenylate Cyclase Type III Is Not a Ubiquitous Marker for All Primary Cilia during Development

Date Published: January 25, 2017

Publisher: Public Library of Science

Author(s): Maria Cristina Antal, Karelle Bénardais, Brigitte Samama, Cyril Auger, Valérie Schini-Kerth, Said Ghandour, Nelly Boehm, Shree Ram Singh.


Adenylate cyclase type III (AC3) is localized in plasma membrane of neuronal primary cilium and can be used as a marker of this cilium. AC3 has also been detected in some other primary cilia such as those of fibroblasts, synoviocytes or astrocytes. Despite the presence of a cilium in almost all cell types, we show that AC3 is not a common marker of all primary cilia of different human and mouse tissues during development. In peripheral organs, AC3 is present mainly in primary cilia in cells of the mesenchymal lineage (fibroblasts, chondroblasts, osteoblasts-osteocytes, odontoblasts, muscle cells and endothelial cells). In epithelia, the apical cilium of renal and pancreatic tubules and of ductal plate in liver is AC3-negative whereas the cilium of basal cells of stratified epithelia is AC3-positive. Using fibroblasts cell culture, we show that AC3 appears at the plasma membrane of the primary cilium as soon as this organelle develops. The functional significance of AC3 localization at the cilium membrane in some cells but not others has to be investigated in relationship with cell physiology and expression at the cilium plasma membrane of specific upstream receptors.

Partial Text

Most differentiated mammalian cells extend a primary cilium. The axoneme of the cilium is made of nine peripheral microtubule doublets (9 + 0) but lacks the two central tubules present in motile cilia. The cilium grows from the mature mother centriole of the diplosome of non-proliferating cells [1, 2]. Primary cilia have chemosensory or mecanosensory functions, according to the specific signaling pathways addressed to the cilium. Pathways implicated in environmental cues detection through membrane receptors have been documented in some cell types including receptor-dependent pathways such as Sonic Hedgehog or non-canonical-Wnt pathways [3, 4], somatostatin receptor 3 [5], serotonin receptor 6 [6], melanin-concentrating hormone receptor 1 [7], dopamine receptor 1 [8], PDGF receptor [9] or extracellular matrix receptors [10].

In different human and mouse tissues, we show that not all primary cilia express the adenylate cyclase type III during development. Adenylate cyclase is the enzyme responsible for synthesis of cAMP from ATP. AC3 was known to be localized to cilia or flagellar structures in adult cells and was first localized to olfactory neurons where it plays a role in the transduction cascade of the olfactory signal through olfactory cilia [11, 12, 13] and in targeting sensory axonal projection to olfactory bulb [19]. Here, we found an early AC3 expression at the tip of the olfactory dendrite in human and mouse, concomitant with the first acetylated-tubulin expression in olfactory cilia.