{"doi":"10.1101/2022.10.18.512810","title":"A microtubule associated protein is essential for malaria parasite transmission","abstract":"ABSTRACT Mature gametocytes of Plasmodium ( P .) falciparum display a banana (falciform) shape conferred by a complex array of subpellicular microtubules (SPMT) associated to the inner membrane complex (IMC). Microtubule associated proteins (MAPs) define MT populations and modulate interaction to pellicular components. Several MAPs have been identified in Toxoplasma gondii and homologues can be found in the genome of Plasmodium species, but the function of these proteins for asexual and sexual development of malaria parasites is still unknown. Here we identified a novel subpellicular MAP, termed SPM3, that is conserved within the genus Plasmodium ., especially within the Laverania subgenus, but absent in other Apicomplexa. Conditional knockdown and targeted gene disruption of Pfspm3 in P. falciparum cause severe morphological defects during gametocytogenesis leading to round, non-falciform gametocytes with an aberrant SPMT pattern. In contrast, Pbspm3 knockout in P. berghei , a species with round gametocytes, caused no defect in gametocytogenesis, but sporozoites displayed an aberrant motility and a dramatic defect in sporozoite invasion of salivary glands leading to a decreased efficiency in transmission. Electron microscopy revealed a dissociation of the SPMT from the IMC in Pbspm3 knockout parasites suggesting a function of SPM3 in anchoring MTs to the IMC. Overall, our results highlight SPM3 as a pellicular component with essential functions for malaria parasite transmission. IMPORTANCE A key structural feature driving the transition between different life cycle stages of the malaria parasite is the unique three membrane “pellicle”, consisting of the parasite plasma membrane (PPM) and a double membrane structure underlying the PPM termed the “inner membrane complex” (IMC). Additionally, there are numerous linearly arranged intramembranous particles (IMPs) linked to the IMC, which likely link the IMC to the subpellicular microtubule cytoskeleton. Here we identify, localize and characterize a novel subpellicular microtubule associated protein unique to the genus Plasmodium ( P .). The knockout of this protein in the human infecting P. falciparum species result in malformed gametocytes and aberrant microtubules. We confirmed the microtubule association in the P. berghei rodent malaria homologue and show that its knockout results in a perturbated microtubule architecture, aberrant sporozoite motility and decreased transmission efficiency.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":300534,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9522,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":991052,"name":"Annika M. Binder","orcid":"0000-0003-2305-4880","position":1,"is_corresponding":false},{"id":686091,"name":"Paolo Mesén-Ramírez","orcid":"0000-0001-7842-5867","position":2,"is_corresponding":false},{"id":991053,"name":"Lilian P. Dorner","orcid":"0000-0002-8120-7155","position":3,"is_corresponding":false},{"id":725553,"name":"Soraya Safavi","orcid":"0000-0001-9989-0952","position":4,"is_corresponding":false},{"id":725550,"name":"Gwendolin Fuchs","orcid":"0000-0001-9294-6984","position":5,"is_corresponding":false},{"id":51379,"name":"Tobias L. Lenz","orcid":"0000-0002-7203-0044","position":6,"is_corresponding":false},{"id":686097,"name":"Anna Bachmann","orcid":"0000-0001-8397-7308","position":7,"is_corresponding":false},{"id":603595,"name":"Danny W. Wilson","orcid":"0000-0002-5073-1405","position":8,"is_corresponding":false},{"id":488735,"name":"Friedrich Frischknecht","orcid":"0000-0002-8332-6668","position":9,"is_corresponding":false},{"id":457027,"name":"Tim‐Wolf Gilberger","orcid":"0000-0002-7965-8272","position":10,"is_corresponding":false},{"id":725548,"name":"Jan Stephan Wichers","orcid":"0000-0002-0599-1742","position":0,"is_corresponding":true}],"reference_count":92,"raw_metadata":null,"created_at":"2026-07-19T00:31:53.559757Z","pmid":null,"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":[]}