Key result
Pharmacological blockade or genetic knockdown of the α1G channel or CaMK4 significantly decreased cell proliferation, migration, and network formation capacity in pulmonary microvascular endothelial cells.
Why the study?
The mechanisms linking α1G-mediated Ca2+ entry to Akt phosphorylation and angiogenic potential in pulmonary microvascular endothelial cells remained incompletely understood.
CaMK4 acts as a downstream effector of α1G-mediated Ca2+ entry to promote the angiogenic potential of pulmonary microvascular endothelial cells independently of the Akt pathway.
Hypothesis-generating for α1G-CaMK4 targeting in pulmonary angiogenesis; should not change practice without human validation.
Pulmonary microvascular endothelial cells (PMVECs) uniquely express an α 1G -subtype of voltage-gated T-type Ca 2+ channel. We have previously revealed that the α 1G channel functions as a background Ca 2+ entry pathway that is critical for the cell proliferation, migration, and angiogenic potential of PMVECs, a novel function attributed to the coupling between α 1G -mediated Ca 2+ entry and constitutive Akt phosphorylation and activation. Despite this significance, mechanism(s) that link the α 1G -mediated Ca 2+ entry to Akt phosphorylation remain incompletely understood. In this study, we demonstrate that Ca 2+ /calmodulin-dependent protein kinase (CaMK) 4 serves as a downstream effector of the α 1G -mediated Ca 2+ entry to promote the angiogenic potential of PMVECs. Notably, CaMK2 and CaMK4 are both expressed in PMVECs. Pharmacological blockade or genetic knockdown of the α 1G channel led to a significant reduction in the phosphorylation level of CaMK4 but not the phosphorylation level of CaMK2. Pharmacological inhibition as well as genetic knockdown of CaMK4 significantly decreased cell proliferation, migration, and network formation capacity in PMVECs. However, CaMK4 inhibition or knockdown did not alter Akt phosphorylation status in PMVECs, indicating that α 1G /Ca 2+ /CaMK4 is independent of the α 1G /Ca 2+ /Akt pathway in sustaining the cells’ angiogenic potential. Altogether, these findings suggest a novel α 1G -CaMK4 signaling complex that regulates the Ca 2+ -dominated angiogenic potential in PMVECs.
No takes yet. Share an insight, caveat, or question.
Zhen et al. (2021) studied this question. Pharmacological blockade or genetic knockdown of the α1G channel or CaMK4 was evaluated on Cell proliferation, migration, and network formation capacity. Pharmacological blockade or genetic knockdown of the α1G channel or CaMK4 significantly decreased cell proliferation, migration, and network formation capacity in pulmonary microvascular endothelial cells.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: