The effects of the disruption of the G-protein subunit Gamma-10 (Gng10) on cell migration and calcium signaling
Bloomsburg University of Pennsylvania
Biological and Allied Health Sciences
G proteins-coupled receptors (GPCRs) play important roles in biological processes such as immune regulation, gene transcription, calcium regulation and the regulation of cell migration. G proteins play crucial roles in transducing GPCR signals to downstream effectors. G proteins are involved in intracellular signaling pathways, including those that control growth, calcium regulation, gene transcription and cell migration. G proteins consist of Gα, Gβ and Gγ subunits. Upon activation, G proteins dissociate into two active molecules, the GαGTP and the Gβγ dimer. Each molecule regulates intracellular signal transduction pathways and elicits cellular responses. Gβγ dimer is a signal transducer that controls various essential effectors in the GPCR pathway. Gβγ dimer controls the activities of PI3K and PLCβ which are crucial for cell migration and calcium signaling. Cell migration is essential for the development and maintenance of multicellular organism and the proper control of Ca2+ signaling is mandatory for effective cell migration. Gγ10 is encoded by the Gng10 gene and a study has found Gng10 to be mutated in uveal melanoma. To determine how disruption of Gng10 would affect migration and calcium signaling, Gng10 was disrupted in CHO-K1 cells using the CRISPR-Cas9 system. Gng10 deficient clones showed a significant reduction in migration ability compared to wild-type cells. Both wild-type and Gng10 deficient clones responded to 10-5 M ATP with no significant difference in the average peak responses. However, Gng10 deficient clones reached their plateau phases at significantly higher levels than wild-type cells. Overall, this finding suggests that Gng10 may have a role in cell migration and calcium signaling but more studies are needed to validate these findings.
G proteins; Cell migration; Cellular signal transduction; Membrane proteins; Bioenergetics; Cellular control mechanisms