{"doi":"10.1083/jcb.202104046","title":"WASP integrates substrate topology and cell polarity to guide neutrophil migration","abstract":"To control their movement, cells need to coordinate actin assembly with the geometric features of their substrate. Here, we uncover a role for the actin regulator WASP in the 3D migration of neutrophils. We show that WASP responds to substrate topology by enriching to sites of inward, substrate-induced membrane deformation. Superresolution imaging reveals that WASP preferentially enriches to the necks of these substrate-induced invaginations, a distribution that could support substrate pinching. WASP facilitates recruitment of the Arp2/3 complex to these sites, stimulating local actin assembly that couples substrate features with the cytoskeleton. Surprisingly, WASP only enriches to membrane deformations in the front half of the cell, within a permissive zone set by WASP's front-biased regulator Cdc42. While WASP KO cells exhibit relatively normal migration on flat substrates, they are defective at topology-directed migration. Our data suggest that WASP integrates substrate topology with cell polarity by selectively polymerizing actin around substrate-induced membrane deformations in the front half of the cell.","journal":"The Journal of Cell Biology","year":2021,"id":156623,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":54,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9551,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":661785,"name":"Gabriele Kockelkoren","orcid":"0000-0001-7405-7411","position":1,"is_corresponding":false},{"id":661786,"name":"Preethi Raghavan","orcid":"0000-0003-4340-3777","position":2,"is_corresponding":false},{"id":659079,"name":"George R. R. Bell","orcid":"0000-0002-1916-8351","position":3,"is_corresponding":false},{"id":661787,"name":"Derek Britain","orcid":"0000-0002-3139-3797","position":4,"is_corresponding":false},{"id":507187,"name":"Natasha Puri","orcid":"0000-0002-4290-4361","position":5,"is_corresponding":false},{"id":567740,"name":"Sean R. Collins","orcid":"0000-0002-4276-5840","position":6,"is_corresponding":false},{"id":109264,"name":"Manuel D. Leonetti","orcid":"0000-0002-4881-405X","position":7,"is_corresponding":false},{"id":469835,"name":"Dimitrios Stamou","orcid":"0000-0001-8456-8995","position":8,"is_corresponding":false},{"id":656841,"name":"Orion D. Weiner","orcid":"0000-0002-1778-6543","position":9,"is_corresponding":false},{"id":656838,"name":"Rachel M. Brunetti","orcid":"0000-0003-4821-3788","position":0,"is_corresponding":true}],"reference_count":130,"raw_metadata":null,"created_at":"2026-07-18T23:44:13.017332Z","pmid":"34964841","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}