Drebrin, a development-associated brain protein from rat embryo, causes the dissociation of tropomyosin from actin filaments.
Drebrin is a development-associated neuroprotein whose cDNA into fibroblasts causes the formation of dendrite-like structures (Shirao, T., Kojima, N., and Obata, K. (1992) Neuroreport 3, 109-112). To explore molecular functions of drebrin during brain development, we purified drebrin from brains of rat embryos. Drebrin bound to actin filaments at a stoichiometry of 1:5 with a dissociation constant (Kd) of 1.2 x 10(-7) M. It strongly inhibited the actin binding activity of tropomyosin. Excess amounts of tropomyosin also inhibited the drebrin binding to actin filaments, suggesting that drebrin and tropomyosin competitively bind to actin filaments. Further, drebrin inhibited not only the actin binding activity of alpha-actinin but also the actin cross-linking activity of alpha-actinin. Gene transfection experiments revealed that tropomyosin was dissociated from actin filaments in drebrin-overexpressing fibroblasts. Thus we hypothesize that drebrin may destabilize actin filaments by dissociating tropomyosin and alpha-actinin from actin filaments, resulting in the formation of axon and dendrites during neuronal development.
Department of Pharmacology, Gunma University School of Medicine, Japan.
R
R
Ishikawa
K
K
Hayashi
T
T
Shirao
Y
Y
Xue
T
T
Takagi
Y
Y
Sasaki
K
K
Kohama
D008841:Actin Cytoskeleton / Q000378:metabolism; D000185:Actinin / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000196:embryology / Q000502:physiology; D003432:Cross-Linking Reagents; D005314:Embryonic and Fetal Development; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000302:isolation & purification / Q000502:physiology*; D011485:Protein Binding; D051381:Rats; D014162:Transfection; D014335:Tropomyosin / Q000378:metabolism*
D000199:Actins; D003432:Cross-Linking Reagents; D009479:Neuropeptides; D014335:Tropomyosin; C053386:drebrins; D000185:Actinin