Journal
MOLECULAR BIOLOGY OF THE CELL
Volume 34, Issue 7, Pages -Publisher
AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E21-08-0386
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Nonmuscle myosin IIB (NMIIB) is a primary force generator during cell motility. Adding back NMIIB and strategic mutants have specific consequences for cell morphology, metabolism, cortical tension, mechanoresponsiveness, and gene expression. Major modes of ATP production and metabolic and growth pathways undergo significant changes in gene expression.
Nonmuscle myosin IIB (NMIIB) is considered a primary force generator during cell motility. Yet many cell types, including motile cells, do not necessarily express NMIIB. Given the potential of cell engineering for the next wave of technologies, adding back NMIIB could be a strategy for creating supercells with strategically altered cell morphology and motility. However, we wondered what unforeseen consequences could arise from such an approach. Here, we leveraged pancreatic cancer cells, which do not express NMIIB. We generated a series of cells where we added back NMIIB and strategic mutants that increase the ADP-bound time or alter the phosphorylation control of bipolar filament assembly. We characterized the cellular phenotypes and conducted RNA-seq analysis. The addition of NMIIB and the different mutants all have specific consequences for cell morphology, metabolism, cortical tension, mechanoresponsiveness, and gene expression. Major modes of ATP production are shifted, including alterations in spare respiratory capacity and the dependence on glycolysis or oxidative phosphorylation. Several metabolic and growth pathways undergo significant changes in gene expression. This work demonstrates that NMIIB is highly integrated with many cellular systems and simple cell engineering has a profound impact that extends beyond the primary contractile activity presumably being added to the cells.
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