THESIS
2015
x, 2-79 pages : illustrations (some color) ; 30 cm
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 mode...[
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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.
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