RhoA/Cdc42 signaling drives cytoplasmic maturation but not endomitosis in megakaryocytes

• DOI: 10.1016/j.celrep.2021.109102
• Publication Date: 2021-05-11T15:54:13Z
• Authors: Tobias Heib; Heike M. Hermanns; Georgi Manukjan; Maximilian Englert; Charly Kusch; Isabelle Carlotta...; Annika Gerber; Lou Martha Wacker...; Philipp Burkard; Thomas Dandekar; Johannes Balkenhol; Daniel Jahn; Sarah Beck; Mara Meub; Sebastian Dütting; Christian Stigloher; Markus Sauer; Deya Cherpokova; Harald Schulze; Cord Brakebusch; Bernhard Nieswandt; Zoltan Nagy; Irina Pleines
• Keywords: CDC42; Small GTPase; Cofilin

Megakaryocytes (MKs), the precursors of blood platelets, are large, polyploid cells residing mainly in bone marrow. We have previously shown that balanced signaling Rho GTPases RhoA and Cdc42 is critical for correct MK localization at marrow sinusoids vivo. Using conditional RhoA/Cdc42 double-knockout (DKO) mice, we reveal here dispensable process polyploidization MKs but essential cytoplasmic maturation. Proplatelet formation virtually abrogated absence leads to severe macrothrombocytopenia DKO animals. The maturation defect associated with downregulation myosin light chain 2 (MLC2) β1-tubulin, as well an upregulation LIM kinase 1 cofilin-1 both mRNA protein level can be linked impaired MKL1/SRF signaling. Our findings demonstrate endomitosis separately regulated processes, latter critically controlled by RhoA/Cdc42.