Decrease in plasminogen activator correlates with synapse elimination during neonatal development of mouse skeletal muscle.
Previous studies have implicated proteases, acting extracellularly, in the mechanism of polyneuronal synapse elimination. Most studies have focused on mammalian, especially rodent, skeletal muscle, where retraction of subordinate nerve terminals occurs during a narrow time window 2-3 weeks after birth. To date no specific protease(s) has been detected that (i) coincides in time with maximal synapse elimination and (ii) is known to act extracellularly on specific extracellular matrix proteins. In previous studies of denervation in adult mouse muscle, rapid activation of urokinase-type plasminogen activator, a neutral serine protease, was detected. This enzyme, by activation of plasminogen to plasmin, specifically degrades matrix components such as fibronectin, type IV collagen, and laminin in muscle. We now present evidence for an initial increase and subsequent decrease in soluble urokinase-type PA--and, to a lesser extent, tissue PA--in developing muscle, suggesting postnatal developmental regulation of these enzymes during the period of maximal synapse elimination. Although considerably higher in specific activity, membrane-bound PA activity followed the wave of synapse elimination, possibly indicating a longer half-life of membrane-bound enzyme(s).
Hantaï
D
D
Neurobiology Research Laboratory, Veterans Administration Medical Center, Kansas City, MO 64128.
Rao
J S
JS
Kahler
C
C
Festoff
B W
BW
D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D002795:Choline O-Acetyltransferase / Q000032:analysis; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D009045:Motor Endplate / Q000502:physiology*; D024510:Muscle Development; D009132:Muscles / Q000201:enzymology / Q000294:innervation; D009469:Neuromuscular Junction / Q000502:physiology*; D010960:Plasminogen Activators / Q000032:analysis*; D010959:Tissue Plasminogen Activator / Q000032:analysis; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis
D002795:Choline O-Acetyltransferase; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator