Receptor desensitization modulates signal relay during Dictyostelium development

Tuesday, October 25, 2011 — Poster Session II
Noon – 2:00 p.m.	Natcher Conference Center	NCI	CELLBIO-2

Authors

• S Das
• EC Rerichae
• A Bagorda
• CA Parent

Abstract

Upon starvation, individual Dictyostelium discoideum cells enter a developmental program that leads to collective group migration and the formation of a multicellular organism. The process is mediated by extracellular cAMP binding to the G protein-coupled cAMP receptor 1 (cAR1), which initiates a signaling cascade leading to the activation of Adenylyl Cyclase A (ACA), the synthesis and secretion of additional cAMP and an autocrine and paracrine activation loop. The release of cAMP allows neighboring cells to polarize and migrate directionally, a process known as chemotaxis, and form characteristic chains of cells called streams. We now report that cAMP relay can be measured biochemically by assessing ACA activity at successive time points after stimulating cells with sub-saturating concentrations of cAMP. We also find that the relay of cAMP signals can be measured by monitoring ERK2 or TORC2 activation. Using mutants exhibiting constitutive PKA activity, we further establish that the capability of cells to relay signals changes during development – a phenomenon that occurs coincidently with the streaming ability of cells during chemotaxis. We propose that as cells proceed through development, the cAMP induced desensitization and downregulation of cAR1 dramatically impacts chemotactic signaling cascades.

back to top