Determining the differential roles of the dock family of GEFs in drosophila development
Abstract
The evolutionarily conserved Dock proteins function as unconventional guanine
nucleotide exchange factors (GEFs). Upon binding to ELMO (Engulfment and cell
motility) proteins, Dock-ELMO complexes activate the Rho family of small GTPases to
mediate a diverse array of biological processes, including cell motility, apoptotic cell
clearance, and axon guidance. Overlapping expression patterns and functional
redundancy among the eleven vertebrate Dock family members, which are subdivided
into four families (Dock-A, B, C, and D), complicate genetic analysis. Drosophila
melanogaster is an excellent genetic model organism to understand Dock protein
function as its genome encodes one ortholog per subfamily: Myoblast city (Mbc; Dock-
A) and Sponge (Spg; Dock-B). The target GTPase of the Dock-A subfamily is Rac,
which modulates actin dynamics. However, the in vivo GTPase downstream of the Dock-
B subfamily remains unclear. Herein we show that the roles of Spg and Mbc are not
redundant in the Drosophila somatic muscle, central nervous system (CNS), or the dorsal
vessel (dv). Moreover, we confirm the in vivo role of Mbc upstream of Rac and provide
evidence that Spg functions in concert with Rap1 to regulate aspects of adhesion.
Together these data show that Mbc and Spg can have differential downstream GTPase
targets. Our findings predict that the ability to regulate downstream GTPases is
dependent on cellular context and allows for the fine-tuning of actin cytoskeletal or cell
adhesion events in biological processes that undergo cell morphogenesis.
Table of Contents
Introduction -- The dock protein sponge binds elmo and functions in drosophila embryonic development -- Differential roles of the unconventional dock family members myoblast city and sponge in drosophila development -- Material and methods -- Discussion
Degree
Ph.D.