| First Author | Heib T | Year | 2021 |
| Journal | Cell Rep | Volume | 35 |
| Issue | 6 | Pages | 109102 |
| PubMed ID | 33979620 | Mgi Jnum | J:323581 |
| Mgi Id | MGI:6717013 | Doi | 10.1016/j.celrep.2021.109102 |
| Citation | Heib T, et al. (2021) RhoA/Cdc42 signaling drives cytoplasmic maturation but not endomitosis in megakaryocytes. Cell Rep 35(6):109102 |
| abstractText | Megakaryocytes (MKs), the precursors of blood platelets, are large, polyploid cells residing mainly in the bone marrow. We have previously shown that balanced signaling of the Rho GTPases RhoA and Cdc42 is critical for correct MK localization at bone marrow sinusoids in vivo. Using conditional RhoA/Cdc42 double-knockout (DKO) mice, we reveal here that RhoA/Cdc42 signaling is dispensable for the process of polyploidization in MKs but essential for cytoplasmic MK maturation. Proplatelet formation is virtually abrogated in the absence of RhoA/Cdc42 and leads to severe macrothrombocytopenia in DKO animals. The MK maturation defect is associated with downregulation of myosin light chain 2 (MLC2) and beta1-tubulin, as well as an upregulation of LIM kinase 1 and cofilin-1 at both the mRNA and protein level and can be linked to impaired MKL1/SRF signaling. Our findings demonstrate that MK endomitosis and cytoplasmic maturation are separately regulated processes, and the latter is critically controlled by RhoA/Cdc42. |
