abi1a (abl-interactor 1a) is one of two zebrafish co-orthologs of vertebrate ABI1, retained from the teleost-specific genome duplication; its paralog is abi1b. It encodes an ABI-family adaptor with an N-terminal WAVE-binding and coiled-coil region, a central proline-rich disordered region and a C-terminal SH3 domain. In mammals ABI1 is a core subunit of the WAVE regulatory complex (SCAR complex), which it assembles and activates to drive Arp2/3-dependent actin polymerization in lamellipodia, and its SH3 domain binds Abl kinases and other signalling partners. The zebrafish protein conserves the WAVE-binding N-terminus, the coiled-coil domain and the SH3 domain. abi1a is expressed at low levels maternally and becomes the predominant ABI1 copy from mid-gastrulation onward, with broad expression across larval and adult tissues. A mosaic F0 CRISPR knockdown did not disturb heart development; no other functional data exist for this copy.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001764 neuron migration | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Neuron migration propagated from PANTHER node PTN000825624, seeded by mouse Abi2 (MGI:106913) and a C. elegans ABI member. Reason: The mouse evidence is for Abi2, whose knockout disturbs neuronal migration in neocortex and hippocampus. WAVE-complex-driven protrusion is a plausible general contributor to neuronal migration, and both zebrafish copies descend from the node, so the IBA is not wrong. It is not a core function of ABI1 (whose mouse knockout phenotype is embryonic heart and brain malformation), and nothing in zebrafish tests it. Kept as non-core; the same action is applied to abi1b. Supporting Evidence: PMID:15572692 Loss of Abi2 also resulted in cell migration defects in the neocortex and hippocampus, abnormal dendritic spine morphology and density, and severe deficits in short- and long-term memory. PMID:21482783 Thus, Abi1-signaling events are not required for gastrulation but are critical during brain and heart development. |
| GO:0005856 cytoskeleton | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoskeleton location mapped from the UniProt subcellular-location vocabulary (ARBA rule). Reason: ABI1 acts at the cortical actin cytoskeleton of protruding membranes as part of the WAVE complex. The term is general but correct; the more informative location is lamellipodium. Supporting Evidence: PMID:15048123 The WAVE2-Abi1-Nap1-PIR121 complex is as active as the WAVE2-Abi1 sub-complex in stimulating Arp2/3, and after Rac activation it is re-localized to the leading edge of ruffles in vivo. |
| GO:0030027 lamellipodium | IBA GO_REF:0000033 | ACCEPT | Summary: Lamellipodium (IBA) from the ABI family node PTN000048906, seeded by fly, mouse and human ABI proteins. Reason: The WAVE complex, of which ABI1 is a core subunit, is recruited to the lamellipodial leading edge, and ABI1 is required for Rac-dependent lamellipodia. The zebrafish protein keeps the WAVE-binding N-terminus and coiled coil, so it is inside the clade that inherited this location; nothing argues for loss. Supporting Evidence: PMID:15048123 Consistently, inhibition of Abi1 by RNA interference (RNAi) abrogates Rac-dependent lamellipodia protrusion. file:DANRE/abi1a/abi1a-bioinformatics/RESULTS.md The N-terminal WAVE-binding region, the coiled-coil domain and the SH3 domain are conserved in both copies |
| GO:0030027 lamellipodium | IEA GO_REF:0000044 | ACCEPT | Summary: Lamellipodium from the UniProt subcellular-location mapping. Reason: Same location as the IBA row, from an independent electronic source; consistent with the mammalian data on WAVE-complex relocalization to the leading edge. Supporting Evidence: PMID:15048123 The WAVE2-Abi1-Nap1-PIR121 complex is as active as the WAVE2-Abi1 sub-complex in stimulating Arp2/3, and after Rac activation it is re-localized to the leading edge of ruffles in vivo. |
| GO:0030175 filopodium | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Filopodium from the UniProt subcellular-location mapping (ARBA rule). Reason: A family-level location transferred by ARBA. The cached literature places ABI1 mainly at lamellipodia and ruffles; I found no cached evidence specific to filopodia and none from zebrafish. Plausible for an adaptor of actin-based protrusions, so kept as a non-core location rather than removed. Supporting Evidence: PMID:15572692 Abi proteins localize to sites of actin polymerization in protrusive membrane structures and regulate actin dynamics in vitro. |
| GO:0031209 SCAR complex | IBA GO_REF:0000033 | ACCEPT | Summary: Membership of the SCAR/WAVE regulatory complex, propagated from the ABI family node (fly, mouse, human, Dictyostelium donors). Reason: This is the defining function of ABI proteins. ABI1 binds the WAVE WHD domain and assembles the pentameric complex, and in the crystal structure the Abi N-terminal helices form a four-helix bundle with WAVE and HSPC300. The WAVE-binding N-terminus is 95% identical between human ABI1 and abi1a, and the coiled-coil domain is fully identical, so the zebrafish copy retains the complex-forming surface. Supporting Evidence: PMID:15048123 Abi1 interacts directly with the WHD domain of WAVE2, increases WAVE2 actin polymerization activity and mediates the assembly of a WAVE2-Abi1-Nap1-PIR121 complex. PMID:21107423 A long four-helix bundle created by a helix from HSPC300 (residues 14-68), two helices from Abi2 (residues 1-39 and 43-112) and a helix from WAVE1 (residues 26-81) contacts Sra1 extensively file:DANRE/abi1a/abi1a-bioinformatics/RESULTS.md The N-terminal WAVE-binding region, the coiled-coil domain and the SH3 domain are conserved in both copies |
| GO:0035591 signaling adaptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Signaling adaptor activity propagated from mouse Abi1 and human ABI1/ABI2. Reason: ABI1 has no enzymatic activity; it bridges upstream signalling proteins (Abl kinases via its SH3 domain, membrane receptors through the WIRS-binding surface it forms with Sra1) to the WAVE complex and Arp2/3-driven actin assembly. Signaling adaptor activity is the most informative molecular function available and matches the conserved domain architecture of abi1a. Supporting Evidence: PMID:7590237 The protein exhibits sequence similarity to homeotic genes, contains several polyproline stretches, and includes a src homology 3 (SH3) domain at its very carboxyl terminus that is required for binding to Abl proteins. PMID:24439376 Structural, biochemical, and cellular studies reveal that a sequence motif that defines these ligands binds to a highly conserved interaction surface of the WRC formed by the Sra and Abi subunits. |
| GO:0098858 actin-based cell projection | IBA GO_REF:0000033 | ACCEPT | Summary: Actin-based cell projection (IBA), the parent of lamellipodium and filopodium. Reason: Correct at a general level, consistent with the lamellipodium annotation; ABI proteins act at protrusive actin structures. Supporting Evidence: PMID:15572692 Abi proteins localize to sites of actin polymerization in protrusive membrane structures and regulate actin dynamics in vitro. |
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Download this section (compressed HTML)Q: Does the maternal/early (abi1b) versus zygotic (abi1a) temporal split reflect a partition of an ancestral ABI1 expression profile, and is gar ABI1 maternally loaded?
Q: Does abi1b upregulate, or compensate, in stable abi1a mutants (PTC versus promoter-less alleles), as the CRISPR F0 study speculated?
Q: Do abi1a and abi1b assemble into the same WAVE complexes (with wasf2, nckap1, cyfip1) in zebrafish tissues where both are expressed?
Experiment: Generate stable abi1a and abi1b mutants (including maternal-zygotic abi1b) and double mutants; score gastrulation cell migration, heart looping and WAVE-complex protein stability (Wasf2, Nckap1 levels).
Hypothesis: abi1a and abi1b are redundant for WAVE-complex function but partitioned in time.
Type: genetic interaction
Experiment: Rescue abi1a mutant (or double mutant) phenotypes with abi1a versus abi1b coding sequence.
Hypothesis: The two proteins are interchangeable.
Type: cross-rescue
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