Document Detail

The prokaryote messenger c-di-GMP triggers stalk cell differentiation in Dictyostelium.
MedLine Citation:
PMID:  22864416     Owner:  NLM     Status:  MEDLINE    
Cyclic di-(3′:5′)-guanosine monophosphate (c-di-GMP) is a major prokaryote signalling intermediate that is synthesized by diguanylate cyclases and triggers sessility and biofilm formation. We detected the first eukaryote diguanylate cyclases in all major groups of Dictyostelia. On food depletion, Dictyostelium discoideum amoebas collect into aggregates, which first transform into migrating slugs and then into sessile fruiting structures. These structures consist of a spherical spore mass that is supported by a column of stalk cells and a basal disk. A polyketide, DIF-1, which induces stalk-like cells in vitro, was isolated earlier. However, its role in vivo proved recently to be restricted to basal disk formation. Here we show that the Dictyostelium diguanylate cyclase, DgcA, produces c-di-GMP as the morphogen responsible for stalk cell differentiation. Dictyostelium discoideum DgcA synthesized c-di-GMP in a GTP-dependent manner and was expressed at the slug tip, which is the site of stalk cell differentiation. Disruption of the DgcA gene blocked the transition from slug migration to fructification and the expression of stalk genes. Fructification and stalk formation were restored by exposing DgcA-null slugs to wild-type secretion products or to c-di-GMP. Moreover, c-di-GMP, but not cyclic di-(3′:5′)-adenosine monophosphate, induced stalk gene expression in dilute cell monolayers. Apart from identifying the long-elusive stalk-inducing morphogen, our work also identifies a role for c-di-GMP in eukaryotes.
Zhi-hui Chen; Pauline Schaap
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Nature     Volume:  488     ISSN:  1476-4687     ISO Abbreviation:  Nature     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-08-30     Completed Date:  2012-10-11     Revised Date:  2014-10-14    
Medline Journal Info:
Nlm Unique ID:  0410462     Medline TA:  Nature     Country:  England    
Other Details:
Languages:  eng     Pagination:  680-3     Citation Subset:  IM    
Data Bank Information
Bank Name/Acc. No.:
GENBANK/JQ676836;  JQ676837
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MeSH Terms
Biological Assay
Cell Differentiation*
Cyclic GMP / analogs & derivatives*,  metabolism
Dictyostelium / cytology*,  genetics,  growth & development,  metabolism*
Fruiting Bodies, Fungal / metabolism
Guanosine Triphosphate / metabolism
Molecular Sequence Data
Prokaryotic Cells / metabolism*
Protozoan Proteins / metabolism
RNA, Messenger / genetics,  metabolism
Second Messenger Systems*
Grant Support
090276//Wellcome Trust; 090276//Wellcome Trust; BB/E016308/1//Biotechnology and Biological Sciences Research Council; BB/G020426//Biotechnology and Biological Sciences Research Council; BB/G020426/1//Biotechnology and Biological Sciences Research Council
Reg. No./Substance:
0/Protozoan Proteins; 0/RNA, Messenger; 61093-23-0/bis(3',5')-cyclic diguanylic acid; 86-01-1/Guanosine Triphosphate; H2D2X058MU/Cyclic GMP

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