RGD Reference Report - The role of microtubule actin cross-linking factor 1 (MACF1) in the Wnt signaling pathway. - Rat Genome Database

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The role of microtubule actin cross-linking factor 1 (MACF1) in the Wnt signaling pathway.

Authors: Chen, HJ  Lin, CM  Lin, CS  Perez-Olle, R  Leung, CL  Liem, RK 
Citation: Chen HJ, etal., Genes Dev. 2006 Jul 15;20(14):1933-45. Epub 2006 Jun 30.
RGD ID: 8553932
Pubmed: PMID:16815997   (View Abstract at PubMed)
PMCID: PMC1522081   (View Article at PubMed Central)
DOI: DOI:10.1101/gad.1411206   (Journal Full-text)

MACF1 (microtubule actin cross-linking factor 1) is a multidomain protein that can associate with microfilaments and microtubules. We found that MACF1 was highly expressed in neuronal tissues and the foregut of embryonic day 8.5 (E8.5) embryos and the head fold and primitive streak of E7.5 embryos. MACF1(-/-) mice died at the gastrulation stage and displayed developmental retardation at E7.5 with defects in the formation of the primitive streak, node, and mesoderm. This phenotype was similar to Wnt-3(-/-) and LRP5/6 double-knockout embryos. In the absence of Wnt, MACF1 associated with a complex that contained Axin, beta-catenin, GSK3beta, and APC. Upon Wnt stimulation, MACF1 appeared to be involved in the translocation and subsequent binding of the Axin complex to LRP6 at the cell membrane. Reduction of MACF1 with small interfering RNA decreased the amount of beta-catenin in the nucleus, and led to an inhibition of Wnt-induced TCF/beta-catenin-dependent transcriptional activation. Similar results were obtained with a dominant-negative MACF1 construct that contained the Axin-binding region. Reduction of MACF1 in Wnt-1-expressing P19 cells resulted in decreased T (Brachyury) gene expression, a DNA-binding transcription factor that is a direct target of Wnt/beta-catenin signaling and required for mesoderm formation. These results suggest a new role of MACF1 in the Wnt signaling pathway.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Macf1Ratpositive regulation of Wnt signaling pathway involved_inIMP PMID:16815997UniProt 

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Ctnnb1Ratmembrane located_inIDA PMID:16815997UniProt 
Gsk3bRatmembrane located_inIDA PMID:16815997UniProt 
Macf1Ratmembrane located_inIDA PMID:16815997UniProt 
Axin1Ratplasma membrane located_inIDA PMID:16815997UniProt 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Axin1Ratprotein binding enablesIPIUniProtKB:D3ZHV2PMID:16815997UniProt 
Macf1Ratprotein binding enablesIPIUniProtKB:O70239PMID:16815997UniProt 
Macf1Ratprotein binding enablesIPIUniProtKB:O75581PMID:16815997UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Axin1  (axin 1)
Ctnnb1  (catenin beta 1)
Gsk3b  (glycogen synthase kinase 3 beta)
Macf1  (microtubule-actin crosslinking factor 1)


Additional Information