Ménage à quatre: profilin regulates axon pathfinding in vivo

Abstract

How an extracellular signal is decoded by the axonal growth cone and transformed to an intracellular signal leading to the appropriate turning or growth response is largely unknown. The highly motile membrane structures (filopodia and lamellipodia) at the tip of the growth cone are supported by a complex cytoskeletal architecture comprising actin and associated proteins. A powerful way to regulate assembly of actin polymers is through proteins, such as profilin, that can sequester monomeric G-actin. Dominant–negative profilin blocks neurite formation in vitro, and Drosophila has proven useful to identify and characterize proteins in vivo that are required for axon pathfinding.Wills et al.1xProfilin and the Abl tyrosine kinase are required for motor axon outgrowth in the Drosophila embryo. Wills, Z., Marr, L., Zinn, K., Goodman, C.S., and Van Vactor, D. Neuron. 1999; 22: 291–299Abstract | Full Text | Full Text PDF | PubMedSee all References1 show that stranded, a previously identified zygotic-lethal mutation, corresponds to profilin/chickadee; motor axon extension and pathfinding are impaired in profilin mutants both in vivo and in vitro. Profilin binds to proteins of the Enabled (Ena) family, which are known to be phosphorylated by the tyrosine kinase Abl. Mutants of profilin and kinase-deficient Abl display an identical axon growth-arrest phenotype of the intersegmental motor neuron b (ISNb), suggesting that Abl and profilin act in the same process; this was further demonstrated by a dose-sensitive genetic analysis. Moreover, inappropriate crossings of axons at the central nervous system midline were observed1xProfilin and the Abl tyrosine kinase are required for motor axon outgrowth in the Drosophila embryo. Wills, Z., Marr, L., Zinn, K., Goodman, C.S., and Van Vactor, D. Neuron. 1999; 22: 291–299Abstract | Full Text | Full Text PDF | PubMedSee all