Abi plays an opposing role to Abl inDrosophilaaxonogenesis and synaptogenesis

Abstract

Abl tyrosine kinase (Abl) regulates axon guidance by modulating actin dynamics. Abelson interacting protein (Abi), originally identified as a kinase substrate of Abl, also plays a key role in actin dynamics, yet its role with respect to Abl in the developing nervous system remains unclear. Here we show that mutations in abi disrupt axonal patterning in the developing Drosophila central nervous system (CNS). However, reducing abi gene dosage by half substantially rescues Abl mutant phenotypes in pupal lethality, axonal guidance defects and locomotion deficits. Moreover, we show that mutations in Abl increase synaptic growth and spontaneous synaptic transmission frequency at the neuromuscular junction. Double heterozygosity for abi and enabled(ena) also suppresses the synaptic overgrowth phenotypes of Abl mutants, suggesting that Abi acts cooperatively with Ena to antagonize Abl function in synaptogenesis. Intriguingly, overexpressing Abi or Ena alone in cultured cells dramatically redistributed peripheral F-actin to the cytoplasm, with aggregates colocalizing with Abi and/or Ena, and resulted in a reduction in neurite extension. However, co-expressing Abl with Abi or Ena redistributed cytoplasmic F-actin back to the cell periphery and restored bipolar cell morphology. These data suggest that abi and Ablhave an antagonistic interaction in Drosophila axonogenesis and synaptogenesis, which possibly occurs through the modulation of F-actin reorganization.

Transcriptomic comparison of Drosophila snRNP biogenesis mutants reveals mutant-specific changes in pre-mRNA processing: implications for spinal muscular atrophy

“…This interaction was recently shown to be required for neurite outgrowth in mammalian cell and zebrafish models of SMA (Li et al 2015). Orthologs of the Abi protein appear to have important roles in neurogenesis via the regulation of actin dynamics (Proepper et al 2007;Lin et al 2009;Liebau et al 2011). Dominant mutations in GARS cause the distal neuropathy Charcot-MarieTooth disease type 2D, and recent observations suggest that GARS may colocalize with SMN in human cells (Motley et al 2010;Drew et al 2011;Grice et al 2015).…”

Abl-interactor-1 (Abi1) has a role in cardiovascular and placental development and is a binding partner of the α4 integrin

“…We showed that homozygous deletion of mouse Abi2 results in abnormal phenotypes in the eye and braintissues with high Abi2 expression (8). Drosophila embryos lacking both maternal and zygotic abi exhibit embryonic lethality and collapse of axonal patterning (20). In contrast to Abi2, Abi1 exhibits widespread expression (8).…”

Disabled is a bona fide component of the Abl signaling network

“…Ena localization is disrupted by the absence of Abl, implying that Ena works downstream of Abl (Grevengoed et al, 2003). Recently, it has been shown that Abl interacting protein 1 (Abi1), first identified biochemically in mammalian cultured cells, acts as an antagonist of Abl signaling during axonogenesis through the modulation of F-actin distribution (Lin et al, 2009).…”