N-cadherin juxtamembrane domain modulates voltage-gated Ca2+ current via RhoA GTPase and Rho-associated kinase Journal Article
| Authors: | Piccoli, G.; Rutishauser, U.; Bruses, J. L. |
| Article Title: | N-cadherin juxtamembrane domain modulates voltage-gated Ca2+ current via RhoA GTPase and Rho-associated kinase |
| Abstract: | The juxtamembrane domain (JMD) of N-cadherin cytoplasmic tail is an important regulatory region of the clustering and adhesion activities of the protein. In addition, the JMD binds a diversity of proteins capable of modifying intracellular processes including cytoskeletal rearrangement mediated by Rho GTPases. These GTPases also function as regulators of voltage-activated calcium channels, which in turn modulate neuronal excitability. The present study was designed to determine whether there is a direct functional link, via Rho GTPase, between the N-cadherin JMD and these voltage-activated channels. It was found that the infusion of the soluble JMD into chick ciliary neurons causes a substantial decrease in the amplitude of the high-threshold voltage-activated (HVA) calcium current. The activation time is increased while the inactivation process is reduced, suggesting that the decreased current amplitude reflects a reduction in the number of channels available to open. This effect was reversed by inhibition of RhoA or its downstream effector, Rho-associated kinase (ROCK). Because ROCK determines the active state of myosin, these results suggest that the modulation of HVA by the JMD could be mediated by changes in the status of the actin-myosin cytoskeleton. |
| Keywords: | controlled study; nonhuman; pyridines; protein domain; protein function; animal cell; animals; actin; animal tissue; enzyme inhibition; embryo; calcium; neurons; phosphorylation; protein processing, post-translational; recombinant fusion proteins; protein-serine-threonine kinases; intracellular signaling peptides and proteins; nerve cell adhesion molecule; rhoa guanine nucleotide binding protein; protein structure, tertiary; cell adhesion; cadherins; myosin; cytoskeleton; nerve cell; amplitude modulation; amides; rho kinase; chick embryo; chickens; guanosine triphosphatase; calcium signaling; patch-clamp techniques; chicken; botulinum toxins; adp ribose transferases; ion channel gating; rhoa gtp-binding protein; ion transport; calcium channels; n-cadherin; priority journal; article; ciliary ganglion neuron; rhoa gtpase; rock; voltage-activated calcium channel; voltage gated calcium channel; membrane current; ganglia, parasympathetic |
| Journal Title: | The Journal of Neuroscience |
| Volume: | 24 |
| Issue: | 48 |
| ISSN: | 0270-6474 |
| Publisher: | Society for Neuroscience |
| Date Published: | 2004-12-01 |
| Start Page: | 10918 |
| End Page: | 10923 |
| Language: | English |
| DOI: | 10.1523/jneurosci.4020-04.2004 |
| PROVIDER: | scopus |
| PUBMED: | 15574742 |
| PMCID: | PMC6730207 |
| DOI/URL: | |
| Notes: | J. Neurosci. -- Cited By (since 1996):23 -- Export Date: 16 June 2014 -- CODEN: JNRSD -- Source: Scopus |
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70Rutishauser
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