Smooth Muscle Myosin Phosphorylated at Single Head Shows Sustained Mechanical Activity

Hiroto Tanaka,Kazuaki Homma,Howard D White,Toshio Yanagida,Mitsuo Ikebe

doi:10.1074/jbc.m710597200

Abstract

Smooth muscle contraction is regulated by the phosphorylation of myosin. It is well known that tonic smooth muscles can maintain force with low energy consumption (latch state); however, the molecular mechanism underlying this phenomenon is unresolved. Here we show that single-head phosphorylated smooth myosin (SHPMII) exhibits fast ( approximately 24 s(-1)) and slow prolonged ( approximately 1 s(-1)) actin interactions, whereas double-head phosphorylated myosin (DHPMII) predominantly exhibits the fast ( approximately 29 s(-1)) interaction, suggesting that the phosphorylated head of SHPMII is mechanically as active as that of DHPMII. Both the fast and the slow actin interactions of SHPMII support the positive net mechanical displacement of actin. The actin translocating velocity of SHPMII was much slower than that of DHPMII, which is consistent with the slow actin interaction of SHPMII. We propose that the "latch state" can be explained by the motor characteristics of SHPMII that is present during the sustained phase of contraction.

Highlights

To examine the motor characteristics of smooth muscle myosin phosphorylated at one head, we prepared smooth muscle myosin species phosphorylated at both heads (DHPMII), phosphorylated at one head (SHPMII), or unphosphorylated (UPMII) (Fig. 1A)
Motor Property of SHPMII—Our result implies that the motor activities of the two heads of SHPMII are distinct from each other; the phosphorylated head is as active as the phosphorylated heads of DHPMII, whereas the unphosphorylated head is partially active in terms of actin translocating activity and the ADP release rate
It should be emphasized that the motor property of the unphosphorylated head of SHPMII is completely different from the unphosphorylated head of UPMII, because both the fast and the slow actomyosin interactions of SHPMII showed positive net displacement in contrast to those of UPMII (Fig. 3, B and C)

Summary

Introduction

Critical roles in the change in dimension of the hollow organs for regulating airflow, blood flow, organ perfusion, filtration rate of glomeruli, and so forth Dysregulation of these smooth muscles causes a variety of pathophysiological states such as asthma and hypertension. Contractions of both phasic and tonic smooth muscles are regulated by the phosphorylation of the regulatory light chain (RLC) of smooth muscle myosin [3,4,5,6,7,8], and the muscle shortening velocity is closely correlated with the extent of the phosphorylation.

Methods

Results

Conclusion