Autocrine Proliferation Inhibition Pathways in Dictyostelium discoideum
Abstract
Very little is known about how tissues can regulate their size. In one possible
mechanism, cells in a tissue secrete a factor that inhibits their proliferation, and as the
tissue gets bigger, the concentration of the factor increases. If the factor reached the
concentration that inhibits proliferation, the resulting negative feedback loop will limit
tissue size. Despite evidence for such factors, very few have been identified and their
signal transduction pathways are poorly understood. Our lab previously found that
Dictyostelium discoideum accumulates such factors, autocrine proliferation repressor
protein A (AprA) and inorganic polyphosphate, to slow or inhibit its proliferation.
Previous work showed that AprA slows the proliferation via an unknown G protein
coupled receptor (GPCR), and polyphosphate inhibits the proliferation using the G
protein coupled receptor GrlD and the Ras GTPase RasC. In this dissertation, I showed
that the GPCR GrlH is required for AprA to slow cell proliferation; I found several
signaling components in the polyphosphate pathway through genetic screens, and
showed that polyphosphate inhibits the proliferation of D. discoideum through an
IP3/Ca²⁺ pathway.
Citation
Tang, Yu (2020). Autocrine Proliferation Inhibition Pathways in Dictyostelium discoideum. Doctoral dissertation, Texas A&M University. Available electronically from https : / /hdl .handle .net /1969 .1 /192460.