Roles of Myosin-interacting Guanine Nucleotide Exchange Factor (MYOGEF) in the Regulation of Membrane Blebbing and Cell Migration
Blebs are rounded membrane protrusions that are involved in many biological processes such as cell migration and apoptosis. The life of a bleb cycle includes bleb initiation, expansion, and retraction. While formation and expansion of blebs is largely driven by hydrostatic pressure, retraction of blebs is believed to be driven by RhoA signaling that leads to the reassembly of the actomyosin network at the bleb membrane. The activity of RhoA at the bleb membrane is inhibited during bleb expansion. However, how RhoA is activated at the bleb membrane is still unclear. RhoA can be activated by guanine nucleotide exchange factors (GEFs). In this study, I investigated the role of a GEF termed myosin II-interacting guanine nucleotide exchange factor (MYOGEF) in membrane blebbing and cell migration. My findings demonstrate that the localization of MYOGEF at the bleb membrane is important for RhoA activation and the reassembly of actomyosin networks at the bleb membrane, thus contributing to bleb retraction. The interaction of MYOGEF with ezrin, a key regulator of membrane blebbing, is essential for the recruitment of MYOGEF to the bleb membrane during bleb retraction. Knockout of MYOGEF or ezrin not only disrupts the localization of MYOGEF to the bleb membrane but also impairs RhoA activation as well as cortex reassembly at the bleb membrane. More importantly, knockout of MYOGEF interferes with bleb retraction and severely decreases cell invasion in both the absence and the presence of the protease inhibitor GM6001. Taken together, my work illustrates a novel regulatory mechanism of MYOGEF for RhoA activation at the bleb membrane to promote bleb retraction. My results also indicate that MYOGEF is required for the amoeboid mode of cell migration. These findings provide critical insights into understanding how membrane blebbing is implicated in the regulation of amoeboid mode of cell migration.
Molecular biology|Cellular biology|Biochemistry
Jiao, Meng, "Roles of Myosin-interacting Guanine Nucleotide Exchange Factor (MYOGEF) in the Regulation of Membrane Blebbing and Cell Migration" (2018). ETD Collection for Fordham University. AAI10808551.