Tuning the Cell's Antenna: Control of Primary Cilia Composition

Cilia are microtubule-based plasma membrane protrusions that are highly conserved from unicellular eukaryotes to humans. Motile cilia function as cellular oars, displacing extracellular fluid, whereas primary cilia function as cell type-specific antennae, detecting chemical, optical or mechanical signals (e.g. neuromodulators, hormones, odorants, morphogens, photons, blood flow, urine flow, etc.).

Defects in primary cilia are implicated in many important diseases, such as cancer, diabetes or Alzheimer's. Moreover, congenital defects in ciliary genes are the central cause of ciliopathies, a diverse group of genetic disorders including polycystic kidney disease, retinitis pigmentosa, and many rare syndromes like Bardet-Biedl or Joubert syndromes. 

Like other antennae, primary cilia must be tuned for proper function. For that, the appropriate receptors and signal transducers must accumulate within the ciliary membrane. In our laboratory, we study the molecular mechanisms of ciliary accumulation for several key ciliary proteins, including GPCRs like HTR6 (a serotonin receptor implicated in many neuropsychiatric conditions) and INPP5E (a phosphoinositide 5-phosphatase whose mutations cause Joubert and other ciliopathy syndromes).