RGD Reference Report - Alpha 4 integrins and vascular cell adhesion molecule-1 play a role in sympathetic innervation of the heart. - Rat Genome Database
Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

Alpha 4 integrins and vascular cell adhesion molecule-1 play a role in sympathetic innervation of the heart.

Authors: Wingerd, KL  Goodman, NL  Tresser, JW  Smail, MM  Leu, ST  Rohan, SJ  Pring, JL  Jackson, DY  Clegg, DO 
Citation: Wingerd KL, etal., J Neurosci 2002 Dec 15;22(24):10772-80.
RGD ID: 628409
Pubmed: (View Article at PubMed) PMID:12486170

Sympathetic neurons innervate the heart early in postnatal development, an event that is crucial for proper modulation of blood pressure and cardiac function. However, the axon guidance cues that direct sympathetic neurons to the heart, and the neuronal receptors that recognize those cues, are poorly understood. Here we present evidence that interactions between the alpha4beta1 integrin on sympathetic neurons and vascular cell adhesion molecule-1 (VCAM-1) in the heart plays a role in cardiac innervation. The alpha4 subunit was detected on postnatal rat superior cervical ganglion (SCG) neurons in culture and in cryosections of SCG and heart. VCAM-1 immunoreactivity was detected on cardiac myocytes that associate with invading sympathetic neurons. Purified recombinant soluble VCAM-1 (rsVCAM-1) stimulated SCG neurite outgrowth at levels comparable with laminin 2/4 and fibronectin (Fn), and outgrowth on rs-VCAM-1 and Fn was blocked by antibodies specific for the alpha4 and beta1 integrin subunits. Intrathoracic injection of function-blocking antibodies to alpha4 and VCAM-1, as well as a small molecule inhibitor of alpha4 integrins, significantly reduced sympathetic innervation of the heart. These results indicate that the interaction between alpha4 integrin and VCAM-1 is important for sympathetic innervation of the heart.

Annotation

Gene Ontology Annotations    

Biological Process

Cellular Component

Objects Annotated

Genes (Rattus norvegicus)
Itga4  (integrin subunit alpha 4)
Vcam1  (vascular cell adhesion molecule 1)


Additional Information