vcla notes (Danio rerio, vinculin a; UniProt B3DI32)
2026-09-28 — session log
Deep research: FAILED for this gene (Edison/Falcon returned 402 Payment Required; the OpenAI key is
invalid). Not retried, per instructions. No -deep-research-*.md file exists; literature research below
was done manually from cached publications and Europe PMC searches.
Accession: B3DI32 (TrEMBL, 1131 aa) holds the ZFIN experimental and IBA GOA rows for vcla. It is the
metavinculin-type isoform (carries the metavinculin insert; see vcla-bioinformatics/RESULTS.md).
Identity and TGD origin
- PANTHER call
TGD_tree (Neopterygii|Teleostei, 1:1, PTHR46180), one gar co-ortholog, two medaka
co-orthologs (projects/DANRE_DUPLICATION/panther_tgd_pairs.tsv).
- Paralog vclb on chr12; vcla on chr13 PMID:28767718
- PMID:28767718
Protein
- Key D1 residue conserved PMID:28767718
- Only notable difference: vclb Y822F PMID:28767718
- My alignment (vcla-bioinformatics): vcla B3DI32 contains the metavinculin insert; Y822 retained in vcla.
Localization
- vcla-GFP in MDCK: focal adhesions + adherens junctions via alpha-catenin VBS PMID:28767718
- Excluded from junctions with alpha-catenin-dVBS PMID:28767718
- Notochord sheath: vcla transcripts enriched PMID:38697108
Expression vs vclb
Mutants
- Han 2017 vcla hu10818 (Δ8, PTC at 160). MZvcla viable, no defects PMID:28767718
- Western: no vclb protein compensation PMID:28767718
- Double (MZvcla; Zvclb) mutants: mild transient cardiac edema, normal skeletal muscle; no adult double mutants PMID:28767718
- Han consider the vcla MO phenotypes (Vogel 2009) most likely non-specific PMID:28767718
- Morpholino (ZDB-MRPHLNO-100114-3) phenotypes: contractile dysfunction (PMID:19800866, PMID:26954676), repolarization (PMID:24952909). These are the basis of the IMP rows for heart contraction, sarcomere organization, repolarization. Disputed by mutants; see review.
Transcriptional adaptation (TA)
- El-Brolosy 2019: vclaΔ13 (bns241) upregulates vclb PMID:30944477
- vclasa14599 (PTC without mRNA decay) no TA PMID:30944477
- NMD dependence tested with upf1 in vcla PMID:30944477
- vcla heterozygotes also adapt PMID:30944477
- Antisense at vclb locus down PMID:30944477
- RNA-less vcla allele (72.44-kb locus deletion) does NOT display TA; wild-type offspring of PTC heterozygotes show inherited vclb upregulation (Jiang 2022) PMID:36427314 PMID:36427314
- Cas13d cleavage of vcla mRNA also raises vclb PMID:40128410
- Key point: TA is triggered by mutant mRNA decay, not by loss of protein. It shows the vclb locus responds to vcla transcript decay; it does not by itself show that Vclb protein substitutes functionally. Han's Western (different PTC allele, hu10818) found no rise in total vinculin protein.
Double mutant vascular phenotypes (both copies)
- PMID:36260739 -- small-molecule leakage; vcla-/-;vclb+/- already affected (dose).
- Kotini 2022 (abstract only): vinculin deletion prevents junctional finger formation in ISVs, rescued by endothelial vinculin PMID:35417696
Heart valve (GOA IMP)
- DN construct derived from vcla head domain PMID:30635353. It blocks vinculin binding partners generally; it does not show which endogenous copy acts. vclb mutants had no strong valve delay.
Decisions summary
- MF (actin filament binding, alpha/beta-catenin binding): accept (IBA/IEA, domain conservation).
- CC focal adhesion, adherens junction, cell-cell contact zone, cytoskeleton: accept.
- MO-based BP (heart contraction, sarcomere organization): UNDECIDED (morpholino vs mutant conflict; Fukuda 2019 reports VCL essential for cardiomyocyte myofilament maturation but abstract does not name paralog/allele).
- Repolarization: MARK_AS_OVER_ANNOTATED.
- AV valve morphogenesis: KEEP_AS_NON_CORE (DN evidence speaks to vinculin, not specifically vcla).
- NEW: establishment of endothelial barrier (GO:0061028), IGI with vclb (PMID:36260739).