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Regulation of vascular smooth muscle tone by N-terminal region of caldesmon: Possible role of tethering actin to myosin

Authors
 Young-Ho Lee  ;  Cynthia Gallant  ;  HongQui Guo  ;  Yanhua Li  ;  C.-L. Albert Wang  ;  Kathleen G. Morgan 
Citation
 Journal of Biological Chemistry, Vol.275(5) : 3213-3220, 2000 
Journal Title
 Journal of Biological Chemistry 
ISSN
 0021-9258 
Issue Date
2000
MeSH
Amino Acid Sequence ; Animals ; Binding Sites ; Calmodulin-Binding Proteins/chemistry ; Calmodulin-Binding Proteins/physiology* ; Cells, Cultured ; Ferrets ; Humans ; Molecular Sequence Data ; Muscle Contraction*/drug effects ; Muscle, Smooth, Vascular/physiology* ; Myosins/chemistry ; Myosins/physiology* ; Peptides/chemistry ; Peptides/pharmacology
Abstract
To assess the functional significance of tethering actin to myosin by caldesmon in the regulation of smooth muscle contraction, we investigated the effects of synthetic peptides, containing the myosin-binding sequences in the N-terminal region of caldesmon, on force directly recorded from single permeabilized smooth muscle cells of ferret portal vein. Two peptides were used, IK29C and MY27C, containing residues from Ile(25) to Lys(53) and from Met(1) to Tyr(27) of the human and chicken caldesmon sequence, respectively, plus an added cysteine at the C terminus. In cells clamped at pCa 6. 7, both peptides increased basal tone. Pretreatment of cells at pCa 6.7 with IK29C or MY27C decreased the amplitude of subsequent phenylephrine-induced contractions but not microcystin-racemic mixture-induced contractions. In all cases the effects of the peptides were concentration-dependent, and IK29C was more potent than MY27C, in agreement with their relative affinity toward myosin. The peptides were ineffective after the phenylephrine contraction was established. MY27C did not further increase the magnitude of contraction caused by a maximally effective concentration of IK29C, consistent with the two peptides having the same mechanism of action. Neither polylysine nor two control peptides containing scrambled sequences of IK29C, which do not bind myosin, had any effect on basal or phenylephrine-induced force. Our results suggest that IK29C and MY27C induce contraction by competing with the myosin-binding domain of endogenous caldesmon. Digital imaging of fluoroisothiocyanate-tagged IK29C confirmed the association of the peptide with intracellular filamentous structures. The results are consistent with a model whereby tethering of actin to myosin by caldesmon may play a role in regulating vascular tone by positioning the C-terminal domain of caldesmon so that it is capable of blocking the actomyosin interaction.
Files in This Item:
T200003289.pdf Download
DOI
10.1074/jbc.275.5.3213
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Physiology (생리학교실) > 1. Journal Papers
Yonsei Authors
Lee, Young Ho(이영호) ORCID logo https://orcid.org/0000-0002-5749-1045
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/171677
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