Two novel members of the ABLIM protein family, ABLIM-2 and -3, associate with STARS and directly bind F-actin.
In addition to regulating cell motility, contractility, and cytokinesis, the actin cytoskeleton plays a critical role in the regulation of transcription and gene expression. We have previously identified a novel muscle-specific actin-binding protein, STARS (striated muscle activator of Rho signaling), which directly binds actin and stimulates serum-response factor (SRF)-dependent transcription. To further dissect the STARS/SRF pathway, we performed a yeast two-hybrid screen of a skeletal muscle cDNA library using STARS as bait, and we identified two novel members of the ABLIM protein family, ABLIM-2 and -3, as STARS-interacting proteins. ABLIM-1, which is expressed in retina, brain, and muscle tissue, has been postulated to function as a tumor suppressor. ABLIM-2 and -3 display distinct tissue-specific expression patterns with the highest expression levels in muscle and neuronal tissue. Moreover, these novel ABLIM proteins strongly bind F-actin, are localized to actin stress fibers, and synergistically enhance STARS-dependent activation of SRF. Conversely, knockdown of endogenous ABLIM expression utilizing small interfering RNA significantly blunted SRF-dependent transcription in C2C12 skeletal muscle cells. These findings suggest that the members of the novel ABLIM protein family may serve as a scaffold for signaling modules of the actin cytoskeleton and thereby modulate transcription.
Barrientos
Tomasa
T
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9148, USA.
Frank
Derk
D
Kuwahara
Koichiro
K
Bezprozvannaya
Svetlana
S
Pipes
G C Teg
GC
Bassel-Duby
Rhonda
R
Richardson
James A
JA
Katus
Hugo A
HA
Olson
Eric N
EN
Frey
Norbert
N
D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D006801:Humans; D060588:LIM Domain Proteins; D051379:Mice; D008840:Microfilament Proteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism; D011485:Protein Binding; D012160:Retina / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D020798:Two-Hybrid System Techniques
C518895:Ablim2 protein, mouse; C518896:Ablim3 protein, mouse; C518897:Abra protein, mouse; D000199:Actins; D060588:LIM Domain Proteins; D008840:Microfilament Proteins