Linked Life Data

16049184

Source:http://linkedlifedata.com/resource/pubmed/id/16049184

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
30
pubmed:dateCreated
2005-7-28
pubmed:abstractText
P/Q-type Ca2+ currents through presynaptic CaV2.1 channels initiate neurotransmitter release, and differential modulation of these channels by neuronal calcium-binding proteins (nCaBPs) may contribute to synaptic plasticity. The nCaBPs calcium-binding protein 1 (CaBP1) and visinin-like protein-2 (VILIP-2) differ from calmodulin (CaM) in that they have an N-terminal myristoyl moiety and one EF-hand that is inactive in binding Ca2+. To determine whether myristoylation contributes to their distinctive modulatory properties, we studied the regulation of CaV2.1 channels by the myristoyl-deficient mutants CaBP1/G2A and VILIP-2/G2A. CaBP1 positively shifts the voltage dependence of CaV2.1 activation, accelerates inactivation, and prevents paired-pulse facilitation in a Ca2+-independent manner. Block of myristoylation abolished these effects, leaving regulation that is similar to endogenous CaM. CaBP1/G2A binds to CaV2.1 with reduced stability, but in situ protein cross-linking and immunocytochemical studies revealed that it binds CaV2.1 in situ and is localized to the plasma membrane by coexpression with CaV2.1, indicating that it binds effectively in intact cells. In contrast to CaBP1, coexpression of VILIP-2 slows inactivation in a Ca2+-independent manner, but this effect also requires myristoylation. These results suggest a model in which nonmyristoylated CaBP1 and VILIP-2 bind to CaV2.1 channels and regulate them like CaM, whereas myristoylation allows differential, Ca2+-independent regulation by the inactive EF-hands of CaBP1 and VILIP-2, which differ in their positions in the protein structure. Differential, myristoylation-dependent regulation of presynaptic Ca2+ channels by nCaBPs may provide a flexible mechanism for diverse forms of short-term synaptic plasticity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
27
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7071-80
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:16049184-Animals, pubmed-meshheading:16049184-Barium, pubmed-meshheading:16049184-Calcium, pubmed-meshheading:16049184-Calcium Channels, N-Type, pubmed-meshheading:16049184-Calcium-Binding Proteins, pubmed-meshheading:16049184-Cells, Cultured, pubmed-meshheading:16049184-Humans, pubmed-meshheading:16049184-Ion Channel Gating, pubmed-meshheading:16049184-Kidney, pubmed-meshheading:16049184-Membrane Potentials, pubmed-meshheading:16049184-Mutagenesis, Site-Directed, pubmed-meshheading:16049184-Myristic Acid, pubmed-meshheading:16049184-Neurocalcin, pubmed-meshheading:16049184-Neuronal Plasticity, pubmed-meshheading:16049184-Neurotransmitter Agents, pubmed-meshheading:16049184-Patch-Clamp Techniques, pubmed-meshheading:16049184-Rats, pubmed-meshheading:16049184-Transfection
pubmed:year
2005
pubmed:articleTitle
Differential regulation of CaV2.1 channels by calcium-binding protein 1 and visinin-like protein-2 requires N-terminal myristoylation.
pubmed:affiliation
Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, N.I.H., Extramural