Rewiring cellular morphology pathways with synthetic guanine nucleotide exchange factors (Nature, 2007, 447:596-600)

報告日期: 2007/11/13
報告時間: 17:10/18:00
報告學生: 卓家楓
講評老師: 郭保麟
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Rewiring cellular morphology pathways with synthetic guanine nucleotide exchange factors

 

Speaker: Cho, Chia-Fong 

Commentator: Prof. Kuo, Pao-Lin

Time: 2007/11/13 17:10-18:00

Place: Room 602

 

Abstract:

   Living cells display complex signal processing behaviors, many of which are mediated by networks of proteins specialized for signal transduction. Eukaryotic cells mobilize the actin cytoskeleton to generate a remarkable diversity of morphological behaviors, including motility, phagocytosis and cytokinesis. Much of this diversity behavior is mediated by guanine nucleotide exchange factors (GEFs) that activate Rho family GTPase. Rho family GTPases are central signaling molecules in the regulation of the actin cytoskeleton. There are over 80 Rho GEFs in the human genome (compared to only 22 genes for the Rho GTPases themselves), and the evolution of new and diverse GEFs is though to provide a mechanism for linking the core cytoskeleton machinery to a wide range of new control inputs. In this paper, the authors test the hypothesis and ask if they can systematically reprogramme cellular morphology by engineering synthetic GEF proteins. They focused on Dbl family Rho GEFs, which have a highly modular structure common to many signaling proteins. The authors generated the synthetic GEFs which recombined the GEF catalytic domain with new regulatory modules and can be activated by non-native inputs. In addition, they have used these synthetic GEFs to reprogramme cellular behaviors in diverse ways. The GEFs can be used to link specific cytoskeleton responses to normally unrelated upstream signaling pathways. Moreover, this strategy could be used to generate a multistep pathway. The multiple synthetic GEFs can be linked as components in series to form an artificial cascade with improve signal processing behavior. These results show the high degree of evolutionary plasticity of this important family of modular signaling proteins, and indicate that it may be possible to use synthetic biology approaches to manipulate the complex spatio-temporal control of cell morphology.

 

Reference:

1. Engineering synthetic signaling proteins with ultrasensitive input/output control. Nat Biotechnol. 2007 Jun; 25(6):660-2. Epub 2007 May 21.

2. Rewiring cell signaling: the logic and plasticity of eukaryotic protein circuitry. Curr Opin Struct Biol. 2004 Dec; 14(6):690-9. Review