Regulation of Vascular Smooth Muscle Tone by N-terminal Region of Caldesmon

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 Ile25 to Lys53 and from Met1 to Tyr27 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 atpCa 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.

• Publication year

  2000

• Venue

  Journal of Biological Chemistry

• Publication date

  2000-02-04

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/JBC.275.5.3213PMID 10652307
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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