Cullin-5 and cullin-2 play a role in the development of neuromuscular junction and the female germ line of Drosophila

Abstract

Cullins confer substrate specificity to E3-ligases which are multi-protein complexes involved in ubiquitin-mediated protein degradation or modification. There are six cullin genes in Drosophila melanogaster. We have raised an antibody against Cul-5 and demonstrated that it expresses in neuronal and non-neuronal cells throughout development. In the embryonic tracheal system, Cul-5 is enriched at fusion sites together with E-Cadherin and Fasciclin III. Mutations of cul-5 do not affect tracheal development but do show defects in the organization of synaptic boutons at the larval neuromuscular junction where the protein is expressed in a subset of motoneuron terminals. Loss of function of another cullin gene 'cul-2' results in similar defects at the larval neuromuscular junction although cul-2;cul-5 double mutants do not show an enhanced phenotype. Both cul-2 and cul-5 mutants show similar aberrations in the development of female germ line. Our results suggest that both of these cullin proteins participate in similar developmental processes.

Reduction of Cullin-2 in somatic cells disrupts differentiation of germline stem cells in the Drosophila ovary

“…Our genetic data identifies Dpp as a target of Cul-2 during ovary development. Earlier reports have shown the importance Cul-5 during the same process (Ayyub, 2011;Kugler et al, 2010aKugler et al, , 2010b. Taken together, these results that indicate that both Cul-5 and Cul-2 are required in ovary development are reminiscent of the data on eye development of Drosophila where both Cul-1 and Cul3 have been shown to be functional (Ou et al, 2002).…”

“…Females of the genotype ptc-Gal4::cul-2RNAi were found to have abnormal follicle formation (Fig. S4A, B) similar to the phenotypes exhibited by the cul-2 loss-of-function mutant (cul-2 EY ) (Ayyub, 2011). Both GSCs and CBs contain a large, membranous, spherical structure called a spectrosome (Lin and Spradling, 1995;Lin and Spradling, 1997;Lin et al, 1994).…”

“…S4A, B) similar to the mutant of cul-2 (Ayyub, 2011). In mammalian systems, Cul-2 protein associates with the VHL tumor suppressor protein and also with ElonginB/ElonginC.…”

“…Protein sequences of Cul-5 and Cul-2 from Drosophila share a very high homology. Moreover, loss of function mutants of these two genes in Drosophila show similar aberrations in neuromuscular junction and in developing egg chambers suggesting some similarities in their functions (Ayyub, 2011;Kugler et al, 2010aKugler et al, , 2010b. Since Gus is known to be an interactor of Cul-5 that is essential in localization of Vasa (Kugler et al, 2010b) and Cul-2 colocalises with Vasa (this report), we wanted to check if Gus interacted with Cul-2 too.…”

“…In Drosophila, loss of function mutation of cul-2 (viz cul-2 EY ) was found to produce follicle cells with aberrant number of nurse cells and cul-2 gene has therefore been implicated in development of egg chambers (Ayyub, 2011). To investigate the role of cul-2 gene during germline cyst development, we have focused mainly on the germarium.…”