Actn4 Links Inactive Integrin α5 With Actin in Zebrafish Somites.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41072919", "kind": "science-record", "revision": 4, "content_hash": "sha256:43ee2bcc8c3df383992519c7301b4499d0547e4d1340a9d5aad10844c34979a4", "created_at": "2026-11-01T20:31:07Z", "updated_at": "2026-11-01T22:57:16Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Actn4 Links Inactive Integrin α5 With Actin in Zebrafish Somites.", "doi": "10.1016/j.mcpro.2025.101087", "pmid": "41072919", "authors": ["Guangyu Sun", "Scott A Holley"], "journal": "Molecular & cellular proteomics : MCP", "year": 2025, "abstract": "Integrins are key plasma membrane proteins that mediate cell-ECM adhesion and communication, and they rely on a conformational change for their activation and bidirectional signaling. However, there are few in vivo studies of integrin activation. Here, we identify Integrin α5 (Itgα5)-associated proteins in the physiological setting of zebrafish somite morphogenesis. Using label-free mass spectrometry, we compared Itgα5-associated proteins in different integrin activation states. As expected, we found active Itgα5 enriched extracellular matrix (ECM) proteins. Surprisingly, inactive Itgα5 incapable of binding ligand recruits actin cytoskeletal proteins as efficiently as the active integrin. We validated Itgα5's linking to actin adaptors using Parallel Reaction Monitoring (PRM). We then focused on α-actinin 4 (Actn4), an actin cross-linker, which we find preferentially associates with inactive Itgα5. Along zebrafish somite boundaries, Itgα5 and Actn4 displayed on and off co-localization, and Actn4 showed a stronger correlation with wild-type and inactive Itgα5 compared with the active Itgα5. We also found that deleting the actin-binding domain (Actn4ABDdel) resulted in cytoplasmic retention and loss of colocalization with Itgα5. These findings suggest that Itgα5 and Actn4 cooperate during somite boundary formation and that actin cytoskeleton reorganization facilitates their colocalization. Furthermore, we showed ligand-binding-deficient Itgα5 associated with Paxillin a (Pxna), a scaffold protein highly enriched at somite boundaries and strongly correlated with activated Itgα5. This study provides novel insights into in vivo integrin activation and integrin-actin interactions and broadens our understanding of integrin's role in tissue morphogenesis. Data are available via ProteomeXchange with identifiers PXD024942, PXD065495, PXD058516, PXD058550, and PXD058747.", "claims": [{"id": "claim-method", "statement": "To compare Itgα5 associated proteins at different activation states (Fig. 2), the differential expression analysis was performed using the R Package limma (version 3.60.5).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41072919", "locator": "sections[21] \"Label-Free Protein Quantification and Statistical Analysis\" paragraph 2", "quote": "To compare Itgα5 associated proteins at different activation states (Fig. 2), the differential expression analysis was performed using the R Package limma (version 3.60.5)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "For label-free mass spectrometry, the mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE (83) partner repository with the dataset identifier PXD024942 and PXD065495.\nFor DIA experiment, the mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD058516.\nFor PRM experiments, the mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD058550. Skyline files have been deposited to PanoramaWeb https://panoramaweb.org/UUff2q.url and associated with the ProteomeXchange identifier PXD058747.\nPublic access will become available once the article is accepted.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41072919", "locator": "sections[43] \"Data Availability\" paragraphs 1-5", "quote": "For label-free mass spectrometry, the mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE (83) partner repository with the dataset identifier PXD024942 and PXD065495.\nFor DIA experiment, the mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD058516.\nFor PRM experiments, the mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD058550. Skyline files have been deposited to PanoramaWeb https://panoramaweb.org/UUff2q.url and associated with the ProteomeXchange identifier PXD058747.\nPublic access will become available once the article is accepted."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Inactive Itgα5 recruits actin cytoskeletal proteins as efficiently as the active integrin.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:41072919", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Surprisingly, inactive Itgα5 incapable of binding ligand recruits actin cytoskeletal proteins as efficiently as the active integrin."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Inactive Itgα5 recruits actin cytoskeletal proteins as efficiently as the active integrin.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:41072919"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:PXD024942"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:PXD024942"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:41072919", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1016/j.mcpro.2025.101087", "sha256": "sha256:ad26933dc3d1e62612c9fe2ce68a343692db333bb4158a0c08c1e17780196702", "bytes": 103913, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1016/j.mcpro.2025.101087", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12860946", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:PXD024942", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=PXD024942", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "PXD024942", "version": null, "note": "For label-free mass spectrometry, the mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE (83) partner repository with the dataset identifier PXD024942 and PXD065495.\nFor DIA experiment, the mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD058516.\nFor PRM experiments, the mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD058550. Skyline files have been deposited to PanoramaWeb https://panoramaweb.org/UUff2q.url and associated with the ProteomeXchange identifier PXD058747.\nPublic access will become available once the article is accepted.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "For label-free mass spectrometry, the mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE (83) partner repository with the dataset identifier PXD024942 and PXD065495.\nFor DIA experiment, the mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD058516.\nFor PRM experiments, the mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD058550. Skyline files have been deposited to PanoramaWeb https://panoramaweb.org/UUff2q.url and associated with the ProteomeXchange identifier PXD058747.\nPublic access will become available once the article is accepted.", "access_statement_kind": "data_availability_statement", "sample_accessions": [], "sample_count": null, "group_sizes": null, "group_sizes_basis": null, "platform": null, "taxon": null, "title": "Proteomic Analysis of Integrin a5 Associated Complexes Dependent upon Integrin Activation State in Zebrafish", "resolution_checked_at": "2026-11-01T20:16:17Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:PXD058516", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=PXD058516", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "PXD058516", "version": null, "note": "For label-free mass spectrometry, the mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE (83) partner repository with the dataset identifier PXD024942 and PXD065495.\nFor DIA experiment, the mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD058516.\nFor PRM experiments, the mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD058550. 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Skyline files have been deposited to PanoramaWeb https://panoramaweb.org/UUff2q.url and associated with the ProteomeXchange identifier PXD058747.\nPublic access will become available once the article is accepted.", "access_statement_kind": "data_availability_statement", "sample_accessions": [], "sample_count": null, "group_sizes": null, "group_sizes_basis": null, "platform": null, "taxon": null, "title": "Proteomics of zebrafish early somites", "resolution_checked_at": "2026-11-01T20:16:18Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:PXD058550", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=PXD058550", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "PXD058550", "version": null, "note": "For label-free mass spectrometry, the mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE (83) partner repository with the dataset identifier PXD024942 and PXD065495.\nFor DIA experiment, the mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD058516.\nFor PRM experiments, the mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD058550. Skyline files have been deposited to PanoramaWeb https://panoramaweb.org/UUff2q.url and associated with the ProteomeXchange identifier PXD058747.\nPublic access will become available once the article is accepted.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "For label-free mass spectrometry, the mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE (83) partner repository with the dataset identifier PXD024942 and PXD065495.\nFor DIA experiment, the mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD058516.\nFor PRM experiments, the mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD058550. Skyline files have been deposited to PanoramaWeb https://panoramaweb.org/UUff2q.url and associated with the ProteomeXchange identifier PXD058747.\nPublic access will become available once the article is accepted.", "access_statement_kind": "data_availability_statement", "sample_accessions": [], "sample_count": null, "group_sizes": null, "group_sizes_basis": null, "platform": null, "taxon": null, "title": "Targeted mass spectrum on activation-state-dependent Integrin alpha 5", "resolution_checked_at": "2026-11-01T20:16:18Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:PXD065495", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=PXD065495", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "PXD065495", "version": null, "note": "For label-free mass spectrometry, the mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE (83) partner repository with the dataset identifier PXD024942 and PXD065495.\nFor DIA experiment, the mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD058516.\nFor PRM experiments, the mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD058550. Skyline files have been deposited to PanoramaWeb https://panoramaweb.org/UUff2q.url and associated with the ProteomeXchange identifier PXD058747.\nPublic access will become available once the article is accepted.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "For label-free mass spectrometry, the mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE (83) partner repository with the dataset identifier PXD024942 and PXD065495.\nFor DIA experiment, the mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD058516.\nFor PRM experiments, the mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD058550. Skyline files have been deposited to PanoramaWeb https://panoramaweb.org/UUff2q.url and associated with the ProteomeXchange identifier PXD058747.\nPublic access will become available once the article is accepted.", "access_statement_kind": "data_availability_statement", "sample_accessions": [], "sample_count": null, "group_sizes": null, "group_sizes_basis": null, "platform": null, "taxon": null, "title": "Proteomic Analysis of Integrin a5 Associated Complexes Dependent upon Integrin Activation State in Zebrafish", "resolution_checked_at": "2026-11-01T20:16:18Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:PXD058747", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=PXD058747", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "PXD058747", "version": null, "note": "For label-free mass spectrometry, the mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE (83) partner repository with the dataset identifier PXD024942 and PXD065495.\nFor DIA experiment, the mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD058516.\nFor PRM experiments, the mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD058550. Skyline files have been deposited to PanoramaWeb https://panoramaweb.org/UUff2q.url and associated with the ProteomeXchange identifier PXD058747.\nPublic access will become available once the article is accepted.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "For label-free mass spectrometry, the mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE (83) partner repository with the dataset identifier PXD024942 and PXD065495.\nFor DIA experiment, the mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD058516.\nFor PRM experiments, the mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD058550. Skyline files have been deposited to PanoramaWeb https://panoramaweb.org/UUff2q.url and associated with the ProteomeXchange identifier PXD058747.\nPublic access will become available once the article is accepted.", "access_statement_kind": "data_availability_statement", "sample_accessions": [], "sample_count": null, "group_sizes": null, "group_sizes_basis": null, "platform": null, "taxon": null, "title": null, "resolution_checked_at": "2026-11-01T20:16:18Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:PXD024942 not downloaded", "asset:data:geo:PXD024942 licence not read", "asset:data:geo:PXD058516 not downloaded", "asset:data:geo:PXD058516 licence not read", "asset:data:geo:PXD058550 not downloaded", "asset:data:geo:PXD058550 licence not read", "asset:data:geo:PXD065495 not downloaded", "asset:data:geo:PXD065495 licence not read", "asset:data:geo:PXD058747 not downloaded", "asset:data:geo:PXD058747 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "To compare Itgα5 associated proteins at different activation states (Fig. 2), the differential expression analysis was performed using the R Package limma (version 3.60.5)."}}, {"id": "method-2", "family": "correlation_analysis", "specific": "pearson", "label": "Correlation analysis", "dsl_operations": ["pearson_r"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 0.8, "band": "high", "quote": "Pearson's correlation"}}], "targets": [], "gaps": []}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: limma_voom."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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However, there are few in vivo studies of integrin activation. Here, we ide", "gα5. This study provides novel insights into in vivo integrin activation and integrin-actin inter"], "order_basis": "paper_text_order:228", "id": "assay:1"}, {"role": "data_generation", "definition_id": "mass_spectrometry", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["afish somite morphogenesis. Using label-free mass spectrometry, we compared Itgα5-associated proteins in di", "iated proteins, rather than for crosslinking mass spectrometry (XL-MS) analysis. Then, the crosslinking rea", "tegrin α5 (Itgα5) activation-state-dependent proteomics experiments and bioinformatics analysis, (2)", "licates, in each state were sent for further proteomic analysis. The proteomic profiles of the inac"], "order_basis": "paper_text_order:407", "id": "assay:2"}, {"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["To compare Itgα5 associated proteins at different activation states (Fig. 2), the differential expression analysis was performed using the R Package limma (version 3.60.5)."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}