Regulation of cross-bridge cycling by Ca2+ in smooth muscle

Arner, Anders; Pfitzer, Gabriele

doi:10.1007/3-540-64753-8_3

Cited by 38 publications

(47 citation statements)

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“…In vitro studies suggest that h-caldesmon modulates the contraction of smooth muscle by inhibiting actomyosin ATPase. The inhibitory effect of h-caldesmon on smoothmuscle contraction can be reversed by binding to Ca 21 / calmodulin or by phosphorylation of caldesmon (Ngai and Walsh 1984;Horiuchi et al 1986;Mak et al 1991;Foster et al 2000; for review see Arner and Pfitzer 1999;Kim et al 2008). h-Caldesmon has gained importance as a smooth-muscle differentiation marker in tumor diagnosis (Miettinen et al 1999;Visée et al 2005), distinguishing myofibroblastic tumors from smooth-muscle tumors (Ceballos et al 2000;Perez-Montiel et al 2006;Qiu et al 2008).…”

Section: Introductionmentioning

confidence: 99%

The Actin-binding Protein Caldesmon Is in Spleen and Lymph Nodes Predominately Expressed by Smooth-muscle Cells, Reticular Cells, and Follicular Dendritic Cells

Köhler

2009

J Histochem Cytochem.

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Reticular cells and follicular dendritic cells (FDCs) build up a framework that underlies the compartmentalization of spleens and lymph nodes. Subpopulations of reticular cells express the smooth-muscle isoform of actin, indicative of a specialized contractile apparatus. We have investigated the distribution of the actin-binding protein caldesmon in spleen and lymph nodes of mice and rats. Caldesmon modulates contraction and regulates cell motility. Alternative splicing of transcripts from a single gene results in high-molecular-mass isoforms ( h-caldesmon) that are predominately expressed by smooth-muscle cells (SMCs), and low-molecular-mass isoforms ( I-caldesmon) that are thought to be widely distributed in non-muscle tissues, but the distribution of caldesmon in spleen and lymph nodes has not been reported. We have performed Western blot analysis and immunohistochemistry using four different antibodies against caldesmon, among these a newly developed polyclonal antibody directed against recombinant mouse caldesmon. Western blot analysis showed the preponderance of I-caldesmon in spleen and lymph nodes. Our results from immunohistochemistry demonstrate caldesmon in SMCs, as expected, but also in reticular cells and FDCs, and suggest that the isoform highly expressed by reticular cells is I-caldesmon. In spleen of SCID mice, caldesmon was expressed by reticular cells in the absence of lymphocytes.

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Section: Introductionmentioning

confidence: 99%

The Actin-binding Protein Caldesmon Is in Spleen and Lymph Nodes Predominately Expressed by Smooth-muscle Cells, Reticular Cells, and Follicular Dendritic Cells

Köhler

2009

J Histochem Cytochem.

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“…The extent of phosphorylation and contraction is modulated by the relative activities of myosin light chain kinase and MLCP (1). These enzymes are influenced by a signaling network of processes in the smooth muscle cell (2,3). The inhibition of MLCP leads to Ca 2ϩ sensitization, i.e.…”

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confidence: 99%

“…In addition, contraction can be regulated by MLC 20 phosphorylation-independent mechanisms, e.g. acting on thin filaments (2,3).…”

mentioning

confidence: 99%

Actions Downstream of Cyclic GMP/Protein Kinase G Can Reverse Protein Kinase C-mediated Phosphorylation of CPI-17 and Ca2+Sensitization in Smooth Muscle

Bonnevier

Arner

2004

Journal of Biological Chemistry

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Ca2؉ sensitivity of smooth muscle contraction is modulated by several systems converging on myosin light chain phosphatase (MLCP). Rho-Rho kinase is considered to inhibit MLCP via phosphorylation, whereas protein kinase C (PKC) induced sensitization has been shown to be dependent on phosphorylation of the inhibitory protein CPI-17. We have explored the interaction of cGMP-dependent protein kinase (PKG) with Ca 2؉ sensitization pathways using permeabilized mouse smooth muscle. Three conditions giving ϳ50% of maximal active force were compared in small intestinal preparations: 1) Ca 2؉ -activated unsensitized muscle (pCa 5.9 with Rho kinase inhibitor Y27632); 2) Rho-Rho kinase-sensitized muscle (pCa 6.1 with guanosine 5-3-O-(thio)triphosphate); and 3) PKC-sensitized muscle (pCa 6.0 with Y27632 and PKC activator phorbol 12,13-dibutyrate). 8-Br-cGMP relaxed the sensitized muscles but had marginal effects on unsensitized preparations, showing that PKG reverses both PKC and Rho-mediated Ca 2؉ sensitization. CPI-17 was present in permeabilized intestinal tissue. In PKC-sensitized preparations, CPI-17 phosphorylation decreased in response to 8-Br-cGMP. The rate of PKC-mediated phosphorylation in the presence of the MLCP inhibitor microcystin-LR was not influenced by 8-Br-cGMP. PKC-induced Ca 2؉ sensitization also was reversed in vascular smooth muscle tissues (portal vein and femoral artery). We conclude that actions downstream of cGMP/PKG can reverse PKC-mediated phosphorylation of CPI-17 and Ca 2؉ sensitization in smooth muscle.Smooth muscle contraction involves a rise in intracellular [Ca 2ϩ ]. The Ca 2ϩ -calmodulin complex activates myosin light chain kinase, which phosphorylates the 20-kDa myosin regulatory light chains (MLC 20 MLCP (PP1M) belongs to the PP1 group of phosphatases and is a heteromeric enzyme consisting of three subunits: a catalytic subunit (PP1M C ); a myosin-targeting subunit (MYPT1); and the M20 subunit (5). MLCP has been reported to be inhibited directly by phosphorylation of its myosin-targeting subunit, MYPT1, on residue Thr-695 performed by Rho kinase (6), MYPT1-associated kinase (sometimes referred to as ZIP-like kinase) (7), and integrin-linked kinase (8). Phosphorylation of MYPT1 at Thr-34 by protein kinase C (PKC) has been shown in vitro (9); the relevance of this result and the effect on the holoenzyme are unknown. MLCP is blocked and inhibited by the binding of the phosphorylated form of protein kinase Cpotentiated inhibitory protein for heterotrimeric myosin light chain phosphatase of 17 kDa (CPI-17). CPI-17 is a major target for phosphorylation by PKC, which phosphorylates the Thr-38 residue. This process has been shown to be crucial for PKCmediated increase in Ca 2ϩ sensitivity of force (Ca 2ϩ sensitization) in smooth muscle (10,36,43). In vitro, Thr-38 on CPI-17 is also phosphorylated by Rho kinase (11), MYPT1-associated kinase (12), protein kinase N (13), integrin-linked kinase (14), p21-activated protein kinase (15), cAMP-activated protein kinase A (16), and cGMP-activated pro...

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“…The thin filament-linked protein caldesmon, the expression of which is higher in adult phasic compared with tonic SM, modulates relaxation kinetics (38). The fact that expression of caldesmon is not reduced in the P0 ileum raises the interesting possibility that caldesmon underlies the faster relaxation rate of the P0 ileum compared with purely tonic fetal gizzard (8) and adult femoral artery (21).…”

Section: Properties Of the Contractile Machinerymentioning

confidence: 99%

Neonatal mouse ileum: functional properties and protein composition of the contractile machinery

et al. 2014

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Background: Immature motility of the ileum may contribute to life-threatening diseases. Little is known about the normal biomechanics of the neonatal ileum in relation to the protein composition of its contractile machinery. Methods: We analyzed the tissue architecture, the biomechanics in intact and β-escin-permeabilized preparations, and the protein composition in neonatal (P0) and adult murine ileum. results: Muscle thickness of the P0 ileum was −50% of the adult ileum and passive compliance was higher. Carbachol-and KCl-elicited contractions were tonic rather than phasic as in the adult. Ca 2+ sensitivity was higher and relaxation rate was slower in β-escin-permeabilized P0 compared with adult ileum. The expression level of β-actin relative to α-actin was higher, and those of total actin, myosin, myosin light chain kinase, the catalytic subunit of myosin phosphatase and telokin were lower compared with the adult. The expression level of MYPT1 was similar, but P0 ileum expressed only the M133; the adult ileum also expressed the M130 isoform. conclusion: The mechanical features and protein composition of the P0 ileum are similar to those of adult tonic smooth muscles. We propose that this is highly adaptive during fetal life allowing the small intestine to act predominantly as a container. d uring development from fetal to newborn and adult life, the gastrointestinal tract (GIT) gradually establishes its mature structure and function. Anatomic features of the digestive tract are present already in human fetal life by 8 wk gestational age (1). However, gastrointestinal motility of preterm individuals is reduced (2). Obviously, this poses severe problems regarding oral food intake which are aggravated by the fact that the immaturity of the GIT, singly or in concert with other perinatal risk factors, may contribute to complications such as spontaneous intestinal perforation, not uncommon in extremely low-birth-weight infants (3). The underlying cause of spontaneous intestinal perforation, one of the leading risk factors of death in neonatal medicine, is still poorly understood. Conceivably an immature intestinal motility is an important determinant leading to stasis of the intestinal contents and overgrowth of infectious enteritis pathogens (4). The ensuing inflammatory response leads to a viscous cycle by not only further impairing of propulsive gut movements but also derogating vascular smooth muscle (SM) function, leading to reduced blood supply and finally to necrosis.Intestinal motility is driven by the concerted action of enteric neurons, pacemaker, and SM cells (2). Although several studies addressed different aspects of the fetal and postnatal maturation of innervation, electrical activity, and global contractile activity of the GIT (5-7), only few studies addressed in some depth the properties of the downstream effector, the SM. Investigations from avian (8) and mammalian stomach (9-11), and guinea pig gallbladder (12) as well as from non-GIT organs like urinary bladder (13,14), revealed major difference...

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Regulation of cross-bridge cycling by Ca2+ in smooth muscle

Cited by 38 publications

References 452 publications

The Actin-binding Protein Caldesmon Is in Spleen and Lymph Nodes Predominately Expressed by Smooth-muscle Cells, Reticular Cells, and Follicular Dendritic Cells

The Actin-binding Protein Caldesmon Is in Spleen and Lymph Nodes Predominately Expressed by Smooth-muscle Cells, Reticular Cells, and Follicular Dendritic Cells

Actions Downstream of Cyclic GMP/Protein Kinase G Can Reverse Protein Kinase C-mediated Phosphorylation of CPI-17 and Ca2+Sensitization in Smooth Muscle

Neonatal mouse ileum: functional properties and protein composition of the contractile machinery

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