Presentación    
REGULATION OF CILIARY
STRUCTURE AND FUNCTION
BY PHOSPHOINOSITIDES
Composition
Name
Position
Institution
Francesc García Gonzalo
Investigador Ramón y Cajal
Universidad Autónoma de Madrid
Raquel Martín Morales
Investigadora Predoctoral
Universidad Autónoma de Madrid
Strategic Objective
Cilia are essential for our health and play important roles in some of our diseases. Our goal is to better understand how cilia work and how they can be manipulated to promote human health.
But what are cilia and why are they important for our health?
Cilia are cell membrane protrusions with an endoskeleton consisting of nine microtubule doublets. This basic architecture, shared by both cilia and flagella, is conserved from unicellular organisms to humans. There are two kinds of cilia: motile and immotile (a.k.a. primary). Motile cilia resemble oars, displacingextracellular fluids. This is how we expel mucus from our bronchi and how sperm swim. Instead, primary cilia behave like antennae, detecting optical, mechanical or chemical signals. Our vision, hearing and smell depend on immotile cilia. Primary cilia also monitor urine flow in the kidney, act as sensors forhunger-controlling hormones in the brain, and control limb and nervous system patterning in the embryo, among many other functions.
Congenital ciliary defects cause ciliopathies, genetically and clinically diverse illnesses whose most common symptoms include mental retardation, retinal degeneration, kidney cysts, polydactyly, obesity, sterility, respiratory infections, and skeletal, heart and brain malformations.Many ciliopathies are rare syndromes (Meckel, Joubert, Bardet-Biedl, Kartagener, etc.), whereas others are more common and affect a single organ (polycystic kidney disease, retinitis pigmentosa).
Ciliopathies are not the only diseases cilia are involved in. Several cancer types, like medulloblastoma and basal cell carcinoma, arise from abnormal activation of Hedgehog signaling, a ciliary pathway essential for embryonic development and adult stem cell function. On the other hand, increasing evidence suggests that cilia modulate the progression of other diseases, such as diabetes and Alzheimer’s.
Given that ciliary function is critically dependent on their composition, our main strategy consists in understanding the molecular mechanisms underlying: (1) ciliary accumulation of the receptors and transducers that sensitize cilia to external stimuli, and (2) the changes in cilia composition whereby ciliary signals are relayed to the rest of the cell.
Research Lines
• Role of phosphoinositides in ciliary signal transduction
• Regulation of cilia composition by phosphoinositides
• Regulation of cilia composition by transition zone proteins
• Factors affecting the ciliary localization of Hedgehog pathway proteins 
• Factors affecting the ciliary localization of polycystic kidney disease proteins