Abstract 132: Alternative Splicing of Bridging Integrator 1 Is a Novel Regulatory Cue for Cardiomyocyte Proliferation
Expanding our knowledge of the genetic pathways of cardiomyocyte proliferation is important to understanding heart formation, disease, and regeneration. Few data exist on the role of multi-domain adaptor proteins in regulating the cardiomyocyte cell cycle. We have identified by RT-PCR a cardiac splice variant of the nucleocytoplasmic adaptor protein, bridging integrator 1 (cBIN1), which is expressed in cardiomyocytes but not in skeletal myocytes (Fig. 1A). We found cBIN1 to be the dominant BIN1 variant of developing mouse cardiomyocytes, and that it is also preferentially located in the nuclei of these immature cells. As the cells mature, the relative abundance of cBIN1 to constitutively expressed variants, by qRT-PCR, decreases from 2.0 in embryonic day 18.5 cardiomyocytes to 0.6 by postnatal day 2 (Fig. 1B). Coincident with altered expression, a majority of cBIN1 redistributes from the nucleus to the cytoplasm and plasma membrane after birth. Moreover, we found that overexpression of exogenous cBIN1 increases the number of actively cycling embryonic cardiomyocytes from 25% to 32%, as assayed by BrdU incorporation and FACS (Fig. 1C). Confirming this result, we found exon-specific siRNA knockdown of cBIN1 suppresses cell proliferation. These studies identify a BIN1 splice variant that exists in cardiac but not skeletal muscle, and that it facilitates cardiomyocyte cell cycle progression during heart maturation.
- © 2012 by American Heart Association, Inc.