{"doi":"10.1002/mrd.23451","title":"Some thoughts about intraflagellar transport in reproduction","abstract":"Cilia/flagella are cell organelles that protrude from the surface of many eukaryotic cells and perform various functions ranging from cell locomotion to sensing environmental stimuli (Satir, 2017). They are divided into primary cilia and motile cilia. Primary cilia have “9 + 0” core axoneme structure and are present in most mammalian cells; the motile cilia have “9 + 2” core axoneme structure and are present in specific cells in the testis, brain, trachea, oviduct, efferent ductules (S. Khan & Scholey, 2018). Cilia are assembled and maintained by a conserved mechanism called intraflagellar transport (IFT), a bidirectional transport process originally discovered in Chlamydomonas (Kozminski et al., 1993). Twenty-two IFT components have been identified so far and these components form IFT-A and IFT-B protein complexes, which contain at least 6 and 16 polypeptides, respectively (Prevo et al., 2017; Rosenbaum & Witman, 2002). These complexes further form a large non-membrane-bound protein complex, termed IFT particles, that lie in close proximity to the basal body and move from the base to the tip of the flagellum, and then back to the base. The BBSome, identified as a protein complex containing eight subunits (Loktev et al., 2008; Nachury et al., 2007), is described to associate with IFT particles to mediate ciliary trafficking of membrane proteins (Wingfield et al., 2018). Including the eight core subunits, 25 Bardet-Biedl Syndrom (BBS)-associated genes have been identified and deficiency of any of them leads to BBS, a special ciliopathy (Rohrschneider & Bolz, 2020). Those IFT particles are thought to carry precursors needed for ciliary/flagellar assembly from the site of synthesis in the cell body to the site of assembly in the cilium/flagellum and the IFT complexes serve as adaptors to mediate contacts between cargo and motor protein. Genetic mouse models provide powerful tools to study the role of IFT in vivo. Like cilia defects, which cause a spectrum of diseases, also called ciliapathies (Ishikawa & Marshall, 2011), disruption of IFT also gives rise to various genetic and developmental disorders (Finetti et al., 2020). Given that cilia play an essential role in embryonic development, global disruption of IFT components causes embryonic lethality, which makes it impossible to use global knockout mice to study the role of IFT in reproduction. An exception is the Ift88 gene. The Oak Ridge Polycystic Kidney (orpk) insertional mutation of the Ift88 gene (Moyer et al., 1994; Pazour et al., 2000), is hypomorphic and is reported to result in the expression of what may be an alternatively spliced messenger RNA (Moyer et al., 1994; Taulman et al., 2001) and a reduced amount of a smaller-than-normal IFT88 protein. This apparently supports sufficient residual IFT to allow the embryo to pass through critical stages in its development, so that some mice homozygous for the mutation survive to birth and even reach adulthood. This mutation is highly disruptive to the ciliary assembly in other organs. The surviving Ift88−/− mice are completely sterile. They produce ∼350-fold fewer sperm than wild-type mice and the remaining sperm completely lack or have very short flagella (Kierszenbaum et al., 2011; San Agustin et al., 2015). The tissue-/cell-specific knockout technique is a game-changer. Using the Stra8-cre transgenic mice, we successfully disrupted Ift20, Ift25, Ift27, Ift140, Ift74, Ift81, and Ift172 (Liu et al., 2017; Qu et al., 2020; Shi et al., 2019; Z. Zhang et al., 2016; Y. Zhang et al., 2017, 2018; S. Zhang et al., 2020) in male germ cells. All these mutant mice were grossly normal, but spermiogenesis and fertility were affected. Studies from these individual IFT knockout mice strongly suggest that functions of these IFTs do not compensate each other. Each IFT component might be responsible for carrying specific cargo proteins for sperm flagella formation. For example, IFT74 and IFT81 are likely more important for carrying tubulin f","journal":"Molecular Reproduction and Development","year":2021,"id":196736,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9594,"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":434628,"name":"Zhibing Zhang","orcid":"0000-0002-7873-7921","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-18T23:50:15.704473Z","pmid":"33507597","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":[]}