Menu

Abl tyrosine kinase signaling regulates the secretory apparatus during axon guidance in Drosophila melanogaster

The Abl tyrosine kinase signaling pathway is essential for neuronal growth cone motility and guidance both in vertebrates and invertebrates. It acts via regulation of the actin cytoskeleton, but how changes in Abl signaling translate into cell morphogenesis remains mysterious. We addressed this problem using a combination of high-resolution STED microscopy, biosensor probes and the innate power of <em>Drosophila</em> genetics. To our surprise we found active Abl nearby Golgi compartment and key Abl effector protein, Enabled, co-localized with the <em>cis</em>- Golgi compartment in the photoreceptor soma of <em>Drosophila</em> photoreceptor neurons. Loss of function of genes that modify Abl signaling caused fragmentation, clumping and altered localization of <em>cis</em> and <em>trans</em>-Golgi, particularly in the basal region of the soma. In addition, we found accumulation of Enabled with Golgi structures in the axon, a feature that is not observed in wild type.  We investigated whether this profound effect of Abl signaling on Golgi structure is a direct influence of Abl, or indirect via its regulation of the actin cytoskeleton. Disruption of actin structure either by genetic or pharmacological approaches in ex-vivo cultured photoreceptors showed similar phenotypes on Golgi structure as observed in Abl mutants. Moreover, epistasis experiments suggested that modification of actin was functionally downstream of Abl in the regulation of Golgi distribution, and thus likely to mediate these effects. This evidence suggests a role of Abl signaling in regulating protein secretion and membrane dynamics separate from its activity in assembling actin cytoskeleton at the leading edge of the growth cone. Remarkably, mutants that disrupt protein secretion and trafficking produce axon guidance defects that mimic those observed in mutants of the Abl signaling pathway. Our findings therefore suggest, first, that Abl signaling controls the structure and localization of the secretory apparatus, and second, that regulation of growth cone motility and guidance by Abl tyrosine kinase is apt to be mediated, in part, by effects on protein secretion and membrane trafficking.