A Model Based on Receptor Desensitization for Cyclic AMP Signaling in Dictyostelium Cells.

Abstract:

:We analyze a model based on receptor modification for the cAMP signaling system that controls aggregation of the slime mold Dictyostelium discoideum after starvation. The model takes into account both the desensitization of the cAMP receptor by reversible phosphorylation and the activation of adenylate cyclase that follows binding of extracellular cAMP to the unmodified receptor. The dynamics of the signaling system is studied in terms of three variables, namely, intracellular and extracellular cAMP, and the fraction of receptor in active state. Using parameter values collected from experimental studies on cAMP signaling and receptor phosphorylation, we show that the model accounts qualitatively and, in a large measure, quantitatively for the various modes of dynamic behavior observed in the experiments: (a) autonomous oscillations of cAMP, (b) relay of suprathreshold cAMP pulses, i.e., excitability, characterized by both an absolute and a relative refractory period, and (c) adaptation to constant cAMP stimuli. A two-variable version of the model is used to demonstrate the link between excitability and oscillations by phase plane analysis. The response of the model to repetitive stimulation allows comprehension, in terms of receptor desensitization, of the role of periodic signaling in Dictyostelium and, more generally, the function of pulsatile patterns of hormone secretion.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Martiel JL,Goldbeter A

doi

10.1016/S0006-3495(87)83275-7

subject

Has Abstract

pub_date

1987-11-01 00:00:00

pages

807-28

issue

5

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(87)83275-7

journal_volume

52

pub_type

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