Exaggerated contraction of airway smooth muscle is the major cause of symptoms in asthma, but the mechanisms that prevent exaggerated contraction are incompletely understood. Here, we showed that integrin α 9 β 1 on airway smooth muscle localizes the polyamine catabolizing enzyme spermidine/spermine N 1 -acetyltransferase (SSAT) in close proximity to the lipid kinase PIP5K1γ. As PIP5K1γ is the major source of PIP2 in airway smooth muscle and its activity is regulated by higher-order polyamines, this interaction inhibited IP3-dependent airway smooth muscle contraction. Mice lacking integrin α 9 β 1 in smooth muscle had increased airway responsiveness in vivo, and loss or inhibition of integrin α 9 β 1 increased in vitro airway narrowing and airway smooth muscle contraction in murine and human airways. Contraction was enhanced in control airways by the higher-order polyamine spermine or by cell-permeable PIP2, but these interventions had no effect on airways lacking integrin α 9 β 1 or treated with integrin α 9 β 1 -blocking antibodies. Enhancement of SSAT activity or knockdown of PIP5K1γ inhibited airway contraction, but only in the presence of functional integrin α 9 β 1 . Therefore, integrin α 9 β 1 appears to serve as a brake on airway smooth muscle contraction by recruiting SSAT, which facilitates local catabolism of polyamines and thereby inhibits PIP5K1γ. Targeting key components of this pathway could thus lead to new treatment strategies for asthma.
The types of myosin light chains in developing fast skeletal muscle of chick embryo were characterized in terms of their mobilities on SDS-polyacrylamide gel electrophoresis and their reactions with antisera against adult fast, slow, or cardiac myosin light chains. Breast and leg muscles of adult chicken mainly contain fast-type myosin, while at early developmental stages, these muscles contain four classes of light chain as judged by SDS-polyacrylamide gel electrophoresis and immunoelectrophoresis; two of these light chains are of the slow and/or cardiac type and the other two are of the fast type. At late developmental stages, fast-type light chains are present in large amounts and slow and/or cardiac light chains exist only in small amounts. It is suggested that the qualitative changes in light chains during embryonic development are coordinated with those in heavy chains reported by Masaki and Yoshizaki (5).
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