Caldesmon smooth muscle contractility regulation

These two phenotypes of smooth muscle, in addition to having marked differences in contractile activity, express different isoforms of several contractile proteins and certain soluble enzymes. In particular, proliferative smooth muscle contains at least three PDPKs p34 i 2 p42 , and p44 PK the contractile phenotype of smooth muscle, only p42 P and p44 mark have been identified. The precise function and a complete description of the substrates for MAPK in the contractile phenotype of smooth muscle are unknown however, one substrate that has been idenhfied is the actin and myosin binding protein, caldesmon. Because of the phosphorylation of cal-desmon, MAPK may be involved in either smooth muscle contractile regulation or the structural organization of actin filaments within smooth muscle cells. 

X. THE ROLE OF CALDESMON IN REGULATING SMOOTH MUSCLE CONTRACTILITY... 

The greatest challenge ahead, because it is the most difficult experimentally, is to determine the physiological role of caldesmon. In vitro experiments show how caldesmon might regulate smooth muscle contractility in concert with myosin phosphorylation, but they can never demonstrate that it does. For this we need new tools that can manipulate caldesmon within the intact cell. It is to be hoped that modern antisense RNA and transgenic techniques could provide the answer. 

Caldesmon (CD) is a ubiquitous protein in smooth muscle cells. The smooth muscle isoform has a sequence-derived molecular mass of 89-93 kDa, but migrates on SDS gels at 120-150 kDa. Within the smooth muscle cell, CD is localized within the contractile apparatus (Furst et al., 1986) and when the contractile filaments are isolated it is found to be tightly bound to the thin filaments (Marston and Lehman, 1985). It is suggested that its in vivo function involves regulation of thin filament activity and possibly a role in the assembly and stabilization of thick and thin filaments. 

Caldesmon has also been shown to inhibit tension development in chemically permeabilized gizzard smooth muscle (Pfitzer etal., 1993). Furthermore, inhibition of caldesmon/F-actin interaction in permeabilized VSM resulted in contractile force generation independently of changes in [Ca +J, supporting the concept that caldesmon may function as a regulator in situ independently of LC20 phosphorylation (Katsuyama et al., 1992). Both caldesmon (Adam et al.,... 

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