Primary cilia are specialized calcium signaling organelles

Primary cilia are solitary nonmotile extensions of the centriole found on nearly all nucleated eukaryotic cells between cell divisions. Only ∼200-300 nm in diameter and a few microns long, they are separated from the cytoplasm by the ciliary neck and basal body. Often called sensory cilia, they are hypothesized to receive chemical and mechanical stimuli and initiate specific cellular signal transduction pathways. When activated by a ligand, Hedgehog (Hh) pathway proteins, such as Gli2 and Smoothened (Smo), translocate from the cell into the cilium(1,2). Mutations in primary ciliary proteins are associated with severe developmental defects(3). The ionic conditions, permeability of the primary cilia membrane, and effectiveness of the diffusion barriers between the cilia and cell body are unknown. Here we show that cilia are a unique calcium compartment regulated by a heteromeric TRP channel, PKD1-L1/PKD2-L1. In contrast to the hypothesis that polycystin (PKD) channels initiate changes in ciliary calcium that are conducted into the cytoplasm(4), we show that changes in ciliary calcium concentration ([Ca(2+)](cilia)) occur without substantially altering global cytoplasmic calcium ([Ca(2+)](cyto)). PKD1-L1/PKD2-L1 acts as a ciliary calcium channel controlling [Ca(2+)](cilia) and thereby modifying Smo-activated Gli2 translocation and Gli1 expression.