Determining the differential roles of the dock family of GEFs in drosophila development

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.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Cell Biology and Biophysics (UMKC)

Grantor

University of Missouri--Kansas City

Year dc:date.issued

2015

Author dc:creator

• Biersmith, Bridget H.

Advisor dc:contributor.advisor

• Geisbrecht, Erika R.

Language dc:language.iso

eng

Handle dc:identifier.uri

https://hdl.handle.net/10355/45540

OAI identifier oai:identifier

oai:mospace.umsystem.edu:10355/45540