Molecular organization of G protein complexes in asymmetric cell division

Abstract

Asymmetric cell division (ACD) is an important characteristic of neural progenitor cells (NPC) during neurogenesis. It has been known that there are two evolutionarily conserved protein complexes involved in regulating ACD, which are the polarity proteins and spindle orientation proteins. The latter group consists of nuclear mitotic apparatus, Gα_i subunit and activator of G protein signaling 3 (AGS3) or G-protein-signaling modulator 2 (GPSM2/LGN). Since G proteins are capable of transducing many different signals, it is important to determine in which state of the Gα_i subunit and how its availability in the cell are regulated through these protein complexes. In order to investigate specifically on neural stem cells, a neural progenitor ENStem-A^TM cell line was employed as a model system for the experiments. As a first step towards characterizing this cell line, expression of the two aforementioned protein complexes during differentiation was monitored. Interestingly, it was found that all components in spindle orientation protein complex are upregulated upon their differentiation into neurons. Particularly, the formation of spindle orientation complex was examined in detail and a new protein known as resistance to inhibitors of cholinesterase 8A (Ric-8A) was found to be involved in this complex. Ric-8A has recently been discovered to have a controversial role on regulating G proteins by promoting nucleotide exchange but represents another candidate to investigate in the regulation of spindle orientation proteins during ACD. The experimental data from my study suggested that both AGS3 and Ric8A interact with the C-terminus of Gα_i3 subunit, which in turn implied that Ric8A may play a role in regulating the formation of spindle orientation protein. Taken together, due to their diverse roles in cellular regulation, the presence of G proteins in the spindle orientation complex may imply a regulatory role in neurogenesis.

Date of Award	2015
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology