Sequestration of pRb by cyclin D3 causes intranuclear reorganization of lamin A/C during muscle cell differentiation.
The A-type lamins that localize in nuclear domains termed lamin speckles are reorganized and antigenically masked specifically during myoblast differentiation. This rearrangement was observed to be linked to the myogenic program as lamin speckles, stained with monoclonal antibody (mAb) LA-2H10, were reorganized in MyoD-transfected fibroblasts induced to transdifferentiate to muscle cells. In C2C12 myoblasts, speckles were reorganized early during differentiation in cyclin D3-expressing cells. Ectopic cyclin D3 induced lamin reorganization in C2C12 myoblasts but not in other cell types. Experiments with adenovirus E1A protein that can bind to and segregate the retinoblastoma protein (pRb) indicated that pRb was essential for the cyclin D3-mediated reorganization of lamin speckles. Cyclin D3-expressing myoblasts displayed site-specific reduction of pRb phosphorylation. Furthermore, disruption of lamin structures by overexpression of lamins inhibited expression of the muscle regulatory factor myogenin. Our results suggest that the reorganization of internal lamins in muscle cells is mediated by key regulators of the muscle differentiation program.
Mariappan
Indumathi
I
Centre for Cellular and Molecular Biology, Hyderabad, India.
Parnaik
Veena K
VK
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D056743:Cyclin D3; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D034904:Lamin Type A / Q000235:genetics / Q000378:metabolism*; D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; D051379:Mice; D024510:Muscle Development; D032446:Myoblasts / Q000166:cytology* / Q000378:metabolism*; D018006:Myogenic Regulatory Factors / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D016160:Retinoblastoma Protein / Q000378:metabolism*
C534696:CCND3 protein, human; D002352:Carrier Proteins; C534697:Ccnd3 protein, mouse; C534698:Ccnd3 protein, rat; D056743:Cyclin D3; D016213:Cyclins; C491310:GRIP1 protein, human; D034904:Lamin Type A; D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; C578040:MEF2C protein, human; C578041:Mef2c protein, mouse; D018006:Myogenic Regulatory Factors; D009419:Nerve Tissue Proteins; D016160:Retinoblastoma Protein; C440308:lamin C