Francesc Garcia Gonzalo: Ciliary Functions of Phosphoinositides

Quan:
15/12/2017 @ 13:00 – 14:30 Europe/Madrid Franja horària
2017-12-15T13:00:00+01:00
2017-12-15T14:30:00+01:00
On:
Pau Viladiu hall (ICO)
ICO
Preu:
0

Orador: Francesc Garcia Gonzalo

El divendres 15 de desembre de 2017 a les 13h, a Sala Pau Viladiu de l’ICO (Hospital Duran i Reynals) tindrà lloc el seminari “Ciliary Functions of Phosphoinositides” a càrrec de Francesc Garcia Gonzalo, PhD (Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM) & Departamento de Bioquímica, Universidad Autónoma de Madrid &

Instituto de Investigación del Hospital Universitario de La Paz (IdiPAZ)). Convidat per José Luis Rosa, PhD.

 

 

Ciliary Signaling Mechanisms
Cilia are microtubule-based plasma membrane protrusions emanating from a specialized centriole known as basal body. Conserved from unicellular eukaryotes to humans, cilia perform motor and/or sensory functions. Sensory cilia, often referred to as primary cilia, specialize in signal reception and transduction. These signals can be optical (photons), mechanical (e.g. blood and urine flow) or chemical (e.g. odorants). Cilia dysfunction causes ciliopathies, diseases that can affect one (e.g. retinitis pigmentosa, polycystic kidney disease) or multiple organs (e.g. Meckel, Joubert, Bardet-Biedl syndromes). Many ciliopathy-associated congenital malformations are due to defects in Hedgehog (Hh) signaling, a ciliary signal transduction pathway essential for embryonic development. In adults, Hh signaling controls stem cell function and its ectopic activation leads to cancer. In our lab, we study the molecular bases of ciliary signaling, with emphasis on the Hh pathway. More precisely, we are addressing these two questions: (1) Role of phosphoinositides in ciliary signaling. We have shown that the ciliary membrane is enriched in PI(4)P and depleted of PI(4,5)P2, and that this is required for optimal Hh responsiveness. Moreover, we have shown that Inpp5e, a ciliopathy-associated ciliary enzyme, is responsible for maintaining ciliary phosphoinositide composition. We now want to understand how these phosphoinositides regulate Hh signaling, and whether they also regulate other ciliary signaling pathways (Ref: Garcia-Gonzalo et al. 2015 Developmental Cell). (2) Role of the transition zone in ciliary signaling. The transition zone (TZ) is the region at the ciliary base separating the cilium from the rest of the cell. We have described a ciliopathy-associated TZ protein complex whose disruption prevents the correct targeting of a number of ciliary membrane proteins, including Inpp5e, Polycystin-2 (mutated in polycystic kidney disease) and Smoothened (whose ciliary accumulation is a key step in Hh pathway activation). We now want to know how these TZ proteins affect the ciliary localization of these signaling proteins (Ref: Garcia-Gonzalo et al. 2011 Nature Genetics).
Ciliary Signaling Mechanisms 
Cilia are microtubule-based plasma membrane protrusions emanating from a specialized centriole known as basal body. Conserved from unicellular eukaryotes to humans, cilia perform motor and/or sensory functions. Sensory cilia, often referred to as primary cilia, specialize in signal reception and transduction. These signals can be optical (photons), mechanical (e.g. blood and urine flow) or chemical (e.g. odorants). Cilia dysfunction causes ciliopathies, diseases that can affect one (e.g. retinitis pigmentosa, polycystic kidney disease) or multiple organs (e.g. Meckel, Joubert, Bardet-Biedl syndromes). Many ciliopathy-associated congenital malformations are due to defects in Hedgehog (Hh) signaling, a ciliary signal transduction pathway essential for embryonic development. In adults, Hh signaling controls stem cell function and its ectopic activation leads to cancer. In our lab, we study the molecular bases of ciliary signaling, with emphasis on the Hh pathway. More precisely, we are addressing these two questions: (1) Role of phosphoinositides in ciliary signaling. We have shown that the ciliary membrane is enriched in PI(4)P and depleted of PI(4,5)P2, and that this is required for optimal Hh responsiveness. Moreover, we have shown that Inpp5e, a ciliopathy-associated ciliary enzyme, is responsible for maintaining ciliary phosphoinositide composition. We now want to understand how these phosphoinositides regulate Hh signaling, and whether they also regulate other ciliary signaling pathways (Ref: Garcia-Gonzalo et al. 2015 Developmental Cell). (2) Role of the transition zone in ciliary signaling. The transition zone (TZ) is the region at the ciliary base separating the cilium from the rest of the cell. We have described a ciliopathy-associated TZ protein complex whose disruption prevents the correct targeting of a number of ciliary membrane proteins, including Inpp5e, Polycystin-2 (mutated in polycystic kidney disease) and Smoothened (whose ciliary accumulation is a key step in Hh pathway activation). We now want to know how these TZ proteins affect the ciliary localization of these signaling proteins (Ref: Garcia-Gonzalo et al. 2011 Nature Genetics).

Tickets: .

Scroll to Top