Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.4.1 (myosin ATPase)
 1,140 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The nerve growth factor protein (NGF) favors polymerization of brain actin and induces its organization to form paracrystalline structures that activate myosin ATPase (ATP phosphohydrolase, EC 3.6.1.3) to an extent greater than actin alone. Binding studies show that the initial 1:1 stoichiometry of NGF-G-actin complexes decreases to 1:7-10 when polymerization is ended and paracrystalline structures are formed. The ratio becomes even lower when heavy meromyosin is added in the absence of ATP, suggesting that heavy meromyosin displaces NGF bound to actin microfilaments. This conclusion is supported by the finding that when heavy meromyosin is added to NGF-microfilament complexes, under conditions for "decorating" microfilaments, the usual paracrystalline structure of the complexes disappears. The NGF-mediated organization of actin and activation of myosin ATPase is visualized as a self-regulatory and self-propagating mechanism, because progressive displacement of the growth factor induced by heavy meromyosin binding to F actin as ATP consumption proceeds renders an increasingly higher amount of NGF free for new interactions. These findings are discussed in the light of the mechanism of action of NGF in the target cells.
 ...
PMID:Nerve growth factor potentiates actomyosin adenosinetriphosphatase. 14 85

The cycling of membrane receptors for substrate-bound proteins via their interaction with the actin cytoskeleton at the leading edge of growth cones and other motile cells is important for neurite outgrowth and cell migration. Receptor delivered to the leading edge binds to its ligand, which induces coupling of the receptor to a rearward flowing network of actin filaments. This coupling is thought to facilitate advance. We show here that a soluble growth factor stimulates this cycling. We have used single particle tracking to monitor the effects of nerve growth factor (NGF) on the movements of beta1 integrin in the plane of the plasma membrane of the filopodia of growth cones. Beta1 integrin was visualized by its binding of 0.2 microm beads coated with a monoclonal Ab directed against an extracellular epitope distant from the binding site for extracellular matrix ligands. The beads were observed by video microscopy. Beads coated with a low concentration of antibody, and therefore bound to unliganded receptor with little cross-linking, showed an increase in both diffusion and directed forward transport in response to NGF. Transport had a net velocity of 37 microm/minute and was characterized by brief periods of sustained forward excursions with a velocity of 75-150 microm/minute. There was a 2-fold increase in the number of beads accumulated at the tips of filopodia after 10 minutes, indicating that NGF enhanced the delivery of beta1 integrin to the periphery. Forward transport was dependent on an intact actin cytoskeleton and myosin ATPase, since treatment with cytochalasin D or the myosin ATPase inhibitor butanedione monoxime inhibited the transport but not the diffusion of receptors. NGF also greatly increased the steady rearward migration of beads coated with a high density of (&bgr;)1 integrin antibody, indicating that coupling of cross-linked receptor to the retrograde flow of actin is also enhanced. The rate of the retrograde flow of actin was unaffected by NGF. These studies show that a soluble factor can stimulate the coupling of a receptor for substrate-bound factor to two actomyosin-based transport mechanisms and thus facilitate the response of the growth cone to the substrate-bound factor by increasing cycling of the receptor at the periphery.
 ...
PMID:Nerve growth factor stimulates coupling of beta1 integrin to distinct transport mechanisms in the filopodia of growth cones. 1093 39