Signal Transduction (IND 447)

Spatial Organization of Signaling

David Yule, Ph.D.

Type-3 InsP₃ Receptors in pancreatic acini: Immunocytochemistry demonstrates that InsP₃ receptors and hence releasable calcium pools are highly localized in the luminal area of this polarized epithelial cell.  Block arrows represent InsP₃ receptors at the luminal pole of the cell, while thin arrows indicate the basolateral boundary of a cluster of cells. 

Release of calcium from the luminal pole of an epithelial cell. Uncaging of InsP₃ throughout a cell with uv light results in a calcium rise which initiates at the luminal pole of a pancreatic acinar cell.  

The fidelity, specificity and efficiency of cellular signals is often defined by the specialized localization or compartmentalization of signaling elements.  This is especially evident for processes which utilize an increase in cytosolic calcium as a primary signal.  At our first meeting we will discuss the structural basis for localized gradients of cytosolic calcium, events which have been reported to occur in cellular sites such as the nucleus, below the plasma membrane, in the luminal pole of secretory epithelia and between cells. In the subsequent meeting, proteins which function as anchoring and scaffolding proteins will be discussed.  These will include scaffolding proteins which are vital to the efficient functioning of the MAP/JUN kinase pathways, a family of anchoring proteins important for protein kinase A signaling and a further class of scaffolding proteins important for the clustering of a diverse number of signaling proteins.  Finally the emerging role of specialized lipid environments in some cells will be addressed.   Through this information the view that the cell does not function as a "black box"; but can spatially limit signals to increase the fidelity and efficiency of signaling will be advanced.