RGD Reference Report - N-cadherin signals through Rac1 determine the localization of connexin 43 in cardiac myocytes. - Rat Genome Database

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N-cadherin signals through Rac1 determine the localization of connexin 43 in cardiac myocytes.

Authors: Matsuda, T  Fujio, Y  Nariai, T  Ito, T  Yamane, M  Takatani, T  Takahashi, K  Azuma, J 
Citation: Matsuda T, etal., J Mol Cell Cardiol. 2006 Apr;40(4):495-502. Epub 2006 Mar 2.
RGD ID: 1582675
Pubmed: PMID:16515795   (View Abstract at PubMed)
DOI: DOI:10.1016/j.yjmcc.2005.12.010   (Journal Full-text)

It has been proposed that the formation of gap junction is influenced by adherens junction in cardiac myocytes. To examine whether signals through N-cadherin are involved in the distribution of connexin 43 (Cx43), the distribution of cell-cell adhesion molecules, N-cadherin and Cx43, was analyzed in aligned cardiac myocytes. To induce cell orientation running in parallel to tension direction, neonatal rat cardiac myocytes were plated for 3 hours and exposed to 20% cyclic stretch for 24 hours on silicone dishes. The aligned cells cultured for 0-5 days were immunostained with anti- N-cadherin or anti-Cx43 antibody. After cultivation for 3-5 days, following the accumulation of N-cadherin, Cx43 was localized at the longitudinal cell termini. Adenoviral gene transfer of dominant negative N-cadherin significantly attenuated the localization of Cx43 at the longitudinal cell termini, suggesting that Cx43 localization is regulated downstream of N-cadherin. In the process of Cx43 localization, Rho family proteins, RhoA and Rac1, were activated, but not Cdc42. RhoA and Rac1 activation was inhibited by the transfection of dominant negative N-cadherin, indicating that RhoA and Rac1 were activated by N-cadherin in the oriented cardiac myocytes. The inhibition of Rho family proteins by Rho GDI significantly attenuated the accumulation of Cx43, but not that of N-cadherin. Furthermore, the translocation of Cx43 to longitudinal cell termini was prevented by the inhibition of Rac1, but not RhoA. Collectively, these findings suggest that the localization of Cx43 was determined through the Rac1 pathway downstream of N-cadherin in cardiac myocytes.




Biological Process

  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
Cdh2Ratregulation of protein localization  IMP  RGD 
Cdh2Ratregulation of Rho protein signal transduction  IMP  RGD 

Cellular Component

  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
Cdh2Ratfascia adherens  IDA  RGD 
Gja1Ratfascia adherens  IDA  RGD 

RGD Manual Annotations


  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
CDH2Humancadherin mediated signaling pathway  ISOCdh2 (Rattus norvegicus) RGD 
Cdh2Mousecadherin mediated signaling pathway  ISOCdh2 (Rattus norvegicus) RGD 
Cdh2Ratcadherin mediated signaling pathway  IMP  RGD 

Genes (Rattus norvegicus)
Cdh2  (cadherin 2) Gja1  (gap junction protein, alpha 1)

Genes (Mus musculus)
Cdh2  (cadherin 2)

Genes (Homo sapiens)
CDH2  (cadherin 2)