Controlling small guanine-nucleotide-exchange factor function through cytoplasmic RNA intramers
作者： G. Mayer , M. Blind , W. Nagel , T. Bohm , T. Knorr
关键词:
摘要: ADP-ribosylation factor (ARF) GTPases and their regulatory proteins have been implicated in the control of diverse biological functions. Two main classes positive elements for ARF discovered so far: large Sec7/Gea small cytohesin/ARNO families, respectively. These harbor guanine-nucleotide-exchange (GEF) activity exerted by common Sec7 domain. The availability a specific inhibitor, fungal metabolite brefeldin A, has enabled documentation involvement GEFs vesicle transport. However, because lack such tools, roles remained controversial. Here, we selected series RNA aptamers that specifically recognize domain cytohesin 1. Some inhibit guanine-nucleotide exchange on ARF1, thereby preventing activation vitro. Among them, aptamer M69 exhibited unexpected specificity GEFs, it does not interact with or GEF related Gea2-Sec7 domain, member class GEFs. inhibitory effect demonstrated vitro clearly is observed as well vivo, based finding produces similar results dominant-negative, GEF-deficient mutant 1: when expressed cytoplasm T-cells, reduces stimulated adhesion to intercellular molecule-1 dramatic reorganization F-actin distribution. highly cellular effects suggest ARF-GEF 1 plays an important role cytoskeletal remodeling events lymphoid cells.
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