{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T05:40:32Z","timestamp":1780378832200,"version":"3.54.1"},"reference-count":52,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,5,4]],"date-time":"2018-05-04T00:00:00Z","timestamp":1525392000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,5,4]],"date-time":"2018-05-04T00:00:00Z","timestamp":1525392000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Inositol hexakisphosphate kinase-1 (IP6K1) is required for male fertility, but the underlying mechanisms have been elusive. Here, we report that IP6K1 is required for multiple aspects of male germ cell development. This development requires selective interactions between germ cells and Sertoli cells, namely apical ectoplasmic specialization. Spermiation (sperm release) requires tubulobulbar complexes. We found that the apical ectoplasmic specialization and tubulobulbar complexes were poorly formed or disrupted in <jats:italic>IP6K1<\/jats:italic> KOs. Deletion of IP6K1 elicited several aberrations, including: 1, sloughing off of round germ cells; 2, disorientation and malformation of elongating\/elongated spermatids; 3, degeneration of acrosomes; 4, defects in germ-Sertoli cell interactions and 5, failure of spermiation. Eventually the sperm cells were not released but phagocytosed by Sertoli cells leading to an absence of sperm in the epididymis.<\/jats:p>","DOI":"10.1038\/s41598-018-25468-8","type":"journal-article","created":{"date-parts":[[2018,4,30]],"date-time":"2018-04-30T10:11:16Z","timestamp":1525083076000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Multiple aspects of male germ cell development and interactions with Sertoli cells require inositol hexakisphosphate kinase-1"],"prefix":"10.1038","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4300-9948","authenticated-orcid":false,"given":"Chenglai","family":"Fu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"Rojas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfred C.","family":"Chin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac A.","family":"Bernstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren K.","family":"Albacarys","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William W.","family":"Wright","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Solomon H.","family":"Snyder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,5,4]]},"reference":[{"key":"25468_CR1","doi-asserted-by":"publisher","first-page":"2349","DOI":"10.1073\/pnas.0712227105","volume":"105","author":"R Bhandari","year":"2008","unstructured":"Bhandari, R., Juluri, K. R., Resnick, A. C. & Snyder, S. H. Gene deletion of inositol hexakisphosphate kinase 1 reveals inositol pyrophosphate regulation of insulin secretion, growth, and spermiogenesis. Proc Natl Acad Sci USA 105, 2349\u20132353, https:\/\/doi.org\/10.1073\/pnas.0712227105 (2008).","journal-title":"Proc Natl Acad Sci USA"},{"key":"25468_CR2","doi-asserted-by":"publisher","first-page":"11056","DOI":"10.1523\/JNEUROSCI.1069-15.2015","volume":"35","author":"C Fu","year":"2015","unstructured":"Fu, C. et al. Inositol Hexakisphosphate Kinase-3 Regulates the Morphology and Synapse Formation of Cerebellar Purkinje Cells via Spectrin\/Adducin. J Neurosci 35, 11056\u201311067, https:\/\/doi.org\/10.1523\/JNEUROSCI.1069-15.201535\/31\/11056 (2015).","journal-title":"J Neurosci"},{"key":"25468_CR3","doi-asserted-by":"publisher","first-page":"1773","DOI":"10.1073\/pnas.1424642112","volume":"112","author":"F Rao","year":"2015","unstructured":"Rao, F. et al. Inositol pyrophosphates promote tumor growth and metastasis by antagonizing liver kinase B1. Proc Natl Acad Sci USA 112, 1773\u20131778, https:\/\/doi.org\/10.1073\/pnas.1424642112 (2015).","journal-title":"Proc Natl Acad Sci USA"},{"key":"25468_CR4","doi-asserted-by":"crossref","unstructured":"Illies, C. et al. Requirement of inositol pyrophosphates for full exocytotic capacity in pancreatic beta cells. Science 318, 1299\u20131302, 318\/5854\/129910.1126\/science.1146824 (2007).","DOI":"10.1126\/science.1146824"},{"key":"25468_CR5","doi-asserted-by":"publisher","first-page":"2036","DOI":"10.1073\/pnas.1700165114","volume":"114","author":"C Fu","year":"2017","unstructured":"Fu, C. et al. Neuronal migration is mediated by inositol hexakisphosphate kinase 1 via alpha-actinin and focal adhesion kinase. Proc Natl Acad Sci USA 114, 2036\u20132041, https:\/\/doi.org\/10.1073\/pnas.1700165114 (2017).","journal-title":"Proc Natl Acad Sci USA"},{"key":"25468_CR6","doi-asserted-by":"publisher","first-page":"1124","DOI":"10.1016\/j.cellsig.2016.04.011","volume":"28","author":"RS Jadav","year":"2016","unstructured":"Jadav, R. S. et al. Deletion of inositol hexakisphosphate kinase 1 (IP6K1) reduces cell migration and invasion, conferring protection from aerodigestive tract carcinoma in mice. Cell Signal 28, 1124\u20131136, https:\/\/doi.org\/10.1016\/j.cellsig.2016.04.011S0898-6568(16)30097-3 (2016).","journal-title":"Cell Signal"},{"key":"25468_CR7","doi-asserted-by":"publisher","first-page":"18970","DOI":"10.1073\/pnas.1309699110","volume":"110","author":"A Burton","year":"2013","unstructured":"Burton, A., Azevedo, C., Andreassi, C., Riccio, A. & Saiardi, A. Inositol pyrophosphates regulate JMJD2C-dependent histone demethylation. Proc Natl Acad Sci USA 110, 18970\u201318975, https:\/\/doi.org\/10.1073\/pnas.1309699110 (2013).","journal-title":"Proc Natl Acad Sci USA"},{"key":"25468_CR8","doi-asserted-by":"crossref","unstructured":"Zhu, Q. et al. Adipocyte-specific deletion of Ip6k1 reduces diet-induced obesity by enhancing AMPK-mediated thermogenesis. J Clin Invest 126, 4273\u20134288, 85510 10.1172\/JCI85510 (2016).","DOI":"10.1172\/JCI85510"},{"key":"25468_CR9","doi-asserted-by":"publisher","first-page":"1973","DOI":"10.1002\/stem.2645","volume":"35","author":"SV Boregowda","year":"2017","unstructured":"Boregowda, S. V. et al. IP6K1 Reduces Mesenchymal Stem\/Stromal Cell Fitness and Potentiates High Fat Diet-Induced Skeletal Involution. Stem Cells 35, 1973\u20131983, https:\/\/doi.org\/10.1002\/stem.2645 (2017).","journal-title":"Stem Cells"},{"key":"25468_CR10","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1016\/j.cell.2010.11.032","volume":"143","author":"A Chakraborty","year":"2010","unstructured":"Chakraborty, A. et al. Inositol pyrophosphates inhibit Akt signaling, thereby regulating insulin sensitivity and weight gain. Cell 143, 897\u2013910, https:\/\/doi.org\/10.1016\/j.cell.2010.11.032S0092-8674(10)01349-8 (2010).","journal-title":"Cell"},{"key":"25468_CR11","doi-asserted-by":"publisher","first-page":"2854","DOI":"10.1242\/jcs.204966","volume":"130","author":"AB Malla","year":"2017","unstructured":"Malla, A. B. & Bhandari, R. IP6K1 is essential for chromatoid body formation and temporal regulation of Tnp2 and Prm2 expression in mouse spermatids. J Cell Sci 130, 2854\u20132866, https:\/\/doi.org\/10.1242\/jcs.204966 (2017).","journal-title":"J Cell Sci"},{"key":"25468_CR12","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.mce.2009.08.004","volume":"315","author":"CY Cheng","year":"2010","unstructured":"Cheng, C. Y., Wong, E. W., Yan, H. H. & Mruk, D. D. Regulation of spermatogenesis in the microenvironment of the seminiferous epithelium: new insights and advances. Mol Cell Endocrinol 315, 49\u201356, https:\/\/doi.org\/10.1016\/j.mce.2009.08.004S0303-7207(09)00408-0 (2010).","journal-title":"Mol Cell Endocrinol"},{"key":"25468_CR13","doi-asserted-by":"crossref","unstructured":"Griswold, M. D. The central role of Sertoli cells in spermatogenesis. Semin Cell Dev Biol 9, 411\u2013416, S1084-9521(98)90203-8 10.1006\/scdb.1998.0203 (1998).","DOI":"10.1006\/scdb.1998.0203"},{"key":"25468_CR14","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1007\/s00018-012-1079-1","volume":"70","author":"MG Alves","year":"2013","unstructured":"Alves, M. G. et al. Hormonal control of Sertoli cell metabolism regulates spermatogenesis. Cell Mol Life Sci 70, 777\u2013793, https:\/\/doi.org\/10.1007\/s00018-012-1079-1 (2013).","journal-title":"Cell Mol Life Sci"},{"key":"25468_CR15","doi-asserted-by":"publisher","first-page":"705","DOI":"10.3892\/mmr.2017.8000","volume":"17","author":"JF Shi","year":"2018","unstructured":"Shi, J. F. et al. Characterization of cholesterol metabolism in Sertoli cells and spermatogenesis (Review). Mol Med Rep 17, 705\u2013713, https:\/\/doi.org\/10.3892\/mmr.2017.8000 (2018).","journal-title":"Mol Med Rep"},{"key":"25468_CR16","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1111\/andr.12165","volume":"4","author":"LR Franca","year":"2016","unstructured":"Franca, L. R., Hess, R. A., Dufour, J. M., Hofmann, M. C. & Griswold, M. D. The Sertoli cell: one hundred fifty years of beauty and plasticity. Andrology 4, 189\u2013212, https:\/\/doi.org\/10.1111\/andr.12165 (2016).","journal-title":"Andrology"},{"key":"25468_CR17","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.semcdb.2014.02.011","volume":"30","author":"G Kaur","year":"2014","unstructured":"Kaur, G., Thompson, L. A. & Dufour, J. M. Sertoli cells\u2013immunological sentinels of spermatogenesis. Semin Cell Dev Biol 30, 36\u201344, https:\/\/doi.org\/10.1016\/j.semcdb.2014.02.011S1084-9521(14)00023-8 (2014).","journal-title":"Semin Cell Dev Biol"},{"key":"25468_CR18","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1002\/ar.1091870307","volume":"187","author":"LD Russell","year":"1977","unstructured":"Russell, L. D. & Clermont, Y. Degeneration of germ cells in normal, hypophysectomized and hormone treated hypophysectomized rats. Anat Rec 187, 347\u2013366, https:\/\/doi.org\/10.1002\/ar.1091870307 (1977).","journal-title":"Anat Rec"},{"key":"25468_CR19","doi-asserted-by":"publisher","first-page":"1673","DOI":"10.1210\/endo-119-4-1673","volume":"119","author":"H Chemes","year":"1986","unstructured":"Chemes, H. The phagocytic function of Sertoli cells: a morphological, biochemical, and endocrinological study of lysosomes and acid phosphatase localization in the rat testis. Endocrinology 119, 1673\u20131681, https:\/\/doi.org\/10.1210\/endo-119-4-1673 (1986).","journal-title":"Endocrinology"},{"key":"25468_CR20","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1002\/aja.1000990307","volume":"99","author":"EF Oakberg","year":"1956","unstructured":"Oakberg, E. F. Duration of spermatogenesis in the mouse and timing of stages of the cycle of the seminiferous epithelium. Am J Anat 99, 507\u2013516, https:\/\/doi.org\/10.1002\/aja.1000990307 (1956).","journal-title":"Am J Anat"},{"key":"25468_CR21","doi-asserted-by":"publisher","first-page":"1593","DOI":"10.1098\/rstb.2009.0251","volume":"365","author":"IA Kopera","year":"2010","unstructured":"Kopera, I. A., Bilinska, B., Cheng, C. Y. & Mruk, D. D. Sertoli-germ cell junctions in the testis: a review of recent data. Philos Trans R Soc Lond B Biol Sci 365, 1593\u20131605, https:\/\/doi.org\/10.1098\/rstb.2009.0251365\/1546\/1593 (2010).","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"key":"25468_CR22","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1093\/humupd\/dmh026","volume":"10","author":"NP Lee","year":"2004","unstructured":"Lee, N. P. & Cheng, C. Y. Ectoplasmic specialization, a testis-specific cell-cell actin-based adherens junction type: is this a potential target for male contraceptive development? Hum Reprod Update 10, 349\u2013369, https:\/\/doi.org\/10.1093\/humupd\/dmh026 (2004).","journal-title":"Hum Reprod Update"},{"key":"25468_CR23","doi-asserted-by":"crossref","unstructured":"Syed, V. & Hecht, N. B. Disruption of germ cell-Sertoli cell interactions leads to spermatogenic defects. Mol Cell Endocrinol 186, 155\u2013157, doi:S0303720701006566 (2002).","DOI":"10.1016\/S0303-7207(01)00656-6"},{"key":"25468_CR24","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1038\/nature02877","volume":"431","author":"G Gliki","year":"2004","unstructured":"Gliki, G., Ebnet, K., Aurrand-Lions, M., Imhof, B. A. & Adams, R. H. Spermatid differentiation requires the assembly of a cell polarity complex downstream of junctional adhesion molecule-C. Nature 431, 320\u2013324, https:\/\/doi.org\/10.1038\/nature02877 (2004).","journal-title":"Nature"},{"key":"25468_CR25","doi-asserted-by":"publisher","first-page":"e1265042","DOI":"10.1080\/21688370.2016.1265042","volume":"4","author":"Q Wen","year":"2016","unstructured":"Wen, Q. et al. Transport of germ cells across the seminiferous epithelium during spermatogenesis-the involvement of both actin- and microtubule-based cytoskeletons. Tissue Barriers 4, e1265042, https:\/\/doi.org\/10.1080\/21688370.2016.1265042 (2016).","journal-title":"Tissue Barriers"},{"key":"25468_CR26","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1016\/B978-0-12-407697-6.00008-8","volume":"303","author":"AW Vogl","year":"2013","unstructured":"Vogl, A. W., Young, J. S. & Du, M. New insights into roles of tubulobulbar complexes in sperm release and turnover of blood-testis barrier. Int Rev Cell Mol Biol 303, 319\u2013355, https:\/\/doi.org\/10.1016\/B978-0-12-407697-6.00008-8 (2013).","journal-title":"Int Rev Cell Mol Biol"},{"key":"25468_CR27","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1002\/ar.1091940205","volume":"194","author":"LD Russell","year":"1979","unstructured":"Russell, L. D. Spermatid-Sertoli tubulobulbar complexes as devices for elimination of cytoplasm from the head region late spermatids of the rat. Anat Rec 194, 233\u2013246, https:\/\/doi.org\/10.1002\/ar.1091940205 (1979).","journal-title":"Anat Rec"},{"key":"25468_CR28","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1095\/biolreprod.104.028803","volume":"71","author":"JA Guttman","year":"2004","unstructured":"Guttman, J. A., Takai, Y. & Vogl, A. W. Evidence that tubulobulbar complexes in the seminiferous epithelium are involved with internalization of adhesion junctions. Biol Reprod 71, 548\u2013559, https:\/\/doi.org\/10.1095\/biolreprod.104.028803 (2004).","journal-title":"Biol Reprod"},{"key":"25468_CR29","doi-asserted-by":"publisher","DOI":"10.1186\/1477-7827-10-27","volume":"10","author":"RD Upadhyay","year":"2012","unstructured":"Upadhyay, R. D., Kumar, A. V., Ganeshan, M. & Balasinor, N. H. Tubulobulbar complex: cytoskeletal remodeling to release spermatozoa. Reprod Biol Endocrinol 10, 27, https:\/\/doi.org\/10.1186\/1477-7827-10-27 (2012).","journal-title":"Reprod Biol Endocrinol"},{"key":"25468_CR30","doi-asserted-by":"crossref","unstructured":"Kusumi, N. et al. Implication of amphiphysin 1 and dynamin 2 in tubulobulbar complex formation and spermatid release. Cell Struct Funct 32, 101\u2013113, JST.JSTAGE\/csf\/07024 (2007).","DOI":"10.1247\/csf.07024"},{"key":"25468_CR31","doi-asserted-by":"publisher","first-page":"1861","DOI":"10.1210\/en.2008-1232","volume":"150","author":"R D\u2019Souza","year":"2009","unstructured":"D\u2019Souza, R. et al. Disruption of tubulobulbar complex by high intratesticular estrogens leading to failed spermiation. Endocrinology 150, 1861\u20131869, https:\/\/doi.org\/10.1210\/en.2008-1232 (2009).","journal-title":"Endocrinology"},{"key":"25468_CR32","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1242\/bio.20122519","volume":"1","author":"JS Young","year":"2012","unstructured":"Young, J. S., De Asis, M., Guttman, J. & Vogl, A. W. Cortactin depletion results in short tubulobulbar complexes and spermiation failure in rat testes. Biol Open 1, 1069\u20131077, https:\/\/doi.org\/10.1242\/bio.20122519 (2012).","journal-title":"Biol Open"},{"key":"25468_CR33","doi-asserted-by":"publisher","first-page":"11411","DOI":"10.1073\/pnas.1001823107","volume":"107","author":"PP Lie","year":"2010","unstructured":"Lie, P. P., Chan, A. Y., Mruk, D. D., Lee, W. M. & Cheng, C. Y. Restricted Arp3 expression in the testis prevents blood-testis barrier disruption during junction restructuring at spermatogenesis. Proc Natl Acad Sci USA 107, 11411\u201311416, https:\/\/doi.org\/10.1073\/pnas.1001823107 (2010).","journal-title":"Proc Natl Acad Sci USA"},{"key":"25468_CR34","doi-asserted-by":"publisher","first-page":"8315","DOI":"10.1073\/pnas.0709854105","volume":"105","author":"DS Johnston","year":"2008","unstructured":"Johnston, D. S. et al. Stage-specific gene expression is a fundamental characteristic of rat spermatogenic cells and Sertoli cells. Proc Natl Acad Sci USA 105, 8315\u20138320, https:\/\/doi.org\/10.1073\/pnas.0709854105 (2008).","journal-title":"Proc Natl Acad Sci USA"},{"key":"25468_CR35","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1111\/j.1365-2605.2010.01089.x","volume":"34","author":"H Cai","year":"2011","unstructured":"Cai, H. et al. Scrotal heat stress causes a transient alteration in tight junctions and induction of TGF-beta expression. Int J Androl 34, 352\u2013362, https:\/\/doi.org\/10.1111\/j.1365-2605.2010.01089.xIJA1089 (2011).","journal-title":"Int J Androl"},{"key":"25468_CR36","doi-asserted-by":"publisher","DOI":"10.1093\/biolre\/iox0423806625","author":"K Lyon","year":"2017","unstructured":"Lyon, K. et al. Ca2+ signaling machinery is present at intercellular junctions and structures associated with junction turnover in rat Sertoli cells. Biol Reprod. https:\/\/doi.org\/10.1093\/biolre\/iox0423806625 (2017).","journal-title":"Biol Reprod"},{"key":"25468_CR37","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1038\/nrendo.2010.71","volume":"6","author":"CY Cheng","year":"2010","unstructured":"Cheng, C. Y. & Mruk, D. D. A local autocrine axis in the testes that regulates spermatogenesis. Nat Rev Endocrinol 6, 380\u2013395, https:\/\/doi.org\/10.1038\/nrendo.2010.71 (2010).","journal-title":"Nat Rev Endocrinol"},{"key":"25468_CR38","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1007\/978-0-387-09597-4_11","volume":"636","author":"AW Vogl","year":"2008","unstructured":"Vogl, A. W., Vaid, K. S. & Guttman, J. A. The Sertoli cell cytoskeleton. Adv Exp Med Biol 636, 186\u2013211, https:\/\/doi.org\/10.1007\/978-0-387-09597-4_11 (2008).","journal-title":"Adv Exp Med Biol"},{"key":"25468_CR39","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1038\/mp.2013.21","volume":"19","author":"A Chakraborty","year":"2014","unstructured":"Chakraborty, A., Latapy, C., Xu, J., Snyder, S. H. & Beaulieu, J. M. Inositol hexakisphosphate kinase-1 regulates behavioral responses via GSK3 signaling pathways. Mol Psychiatry 19, 284\u2013293, https:\/\/doi.org\/10.1038\/mp.2013.21 (2014).","journal-title":"Mol Psychiatry"},{"key":"25468_CR40","doi-asserted-by":"publisher","first-page":"16005","DOI":"10.1073\/pnas.1417900111","volume":"111","author":"F Rao","year":"2014","unstructured":"Rao, F. et al. Inositol hexakisphosphate kinase-1 mediates assembly\/disassembly of the CRL4-signalosome complex to regulate DNA repair and cell death. Proc Natl Acad Sci USA 111, 16005\u201316010, https:\/\/doi.org\/10.1073\/pnas.1417900111 (2014).","journal-title":"Proc Natl Acad Sci USA"},{"key":"25468_CR41","doi-asserted-by":"crossref","unstructured":"Ghoshal, S., Tyagi, R., Zhu, Q. & Chakraborty, A. Inositol hexakisphosphate kinase-1 interacts with perilipin1 to modulate lipolysis. Int J Biochem Cell Biol 78, 149\u2013155, S1357-2725(16)30158-3 10.1016\/j.biocel.2016.06.018 (2016).","DOI":"10.1016\/j.biocel.2016.06.018"},{"key":"25468_CR42","doi-asserted-by":"crossref","unstructured":"Zhang, J. et al. Regulation of Sertoli-germ cell adherens junction dynamics via changes in protein-protein interactions of the N-cadherin-beta-catenin protein complex which are possibly mediated by c-Src and myotubularin-related protein 2: an in vivo study using an androgen suppression model. Endocrinology 146, 1268\u20131284, en.2004-1194 10.1210\/en.2004-1194 (2005).","DOI":"10.1210\/en.2004-1194"},{"key":"25468_CR43","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1002\/bies.20513","volume":"29","author":"HH Yan","year":"2007","unstructured":"Yan, H. H., Mruk, D. D., Lee, W. M. & Cheng, C. Y. Ectoplasmic specialization: a friend or a foe of spermatogenesis? Bioessays 29, 36\u201348, https:\/\/doi.org\/10.1002\/bies.20513 (2007).","journal-title":"Bioessays"},{"key":"25468_CR44","doi-asserted-by":"publisher","first-page":"99","DOI":"10.4161\/spmg.1.2.16913","volume":"1","author":"CY Cheng","year":"2011","unstructured":"Cheng, C. Y. & Mruk, D. D. Actin binding proteins and spermiogenesis: Some unexpected findings. Spermatogenesis 1, 99\u2013104, https:\/\/doi.org\/10.4161\/spmg.1.2.169132156-5554-1-2-4 (2011).","journal-title":"Spermatogenesis"},{"key":"25468_CR45","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1679\/aohc.67.271","volume":"67","author":"AL Kierszenbaum","year":"2004","unstructured":"Kierszenbaum, A. L. & Tres, L. L. The acrosome-acroplaxome-manchette complex and the shaping of the spermatid head. Arch Histol Cytol 67, 271\u2013284 (2004).","journal-title":"Arch Histol Cytol"},{"key":"25468_CR46","doi-asserted-by":"publisher","first-page":"95","DOI":"10.4161\/spmg.1.2.16820","volume":"1","author":"G Berruti","year":"2011","unstructured":"Berruti, G. & Paiardi, C. Acrosome biogenesis: Revisiting old questions to yield new insights. Spermatogenesis 1, 95\u201398, https:\/\/doi.org\/10.4161\/spmg.1.2.168202156-5554-1-2-3 (2011).","journal-title":"Spermatogenesis"},{"key":"25468_CR47","doi-asserted-by":"publisher","first-page":"3031","DOI":"10.1042\/BCJ20160610","volume":"473","author":"M Chanduri","year":"2016","unstructured":"Chanduri, M. et al. Inositol hexakisphosphate kinase 1 (IP6K1) activity is required for cytoplasmic dynein-driven transport. Biochem J 473, 3031\u20133047, https:\/\/doi.org\/10.1042\/BCJ20160610 (2016).","journal-title":"Biochem J"},{"key":"25468_CR48","doi-asserted-by":"publisher","first-page":"e979623","DOI":"10.4161\/21565562.2014.979623","volume":"4","author":"L O\u2019Donnell","year":"2014","unstructured":"O\u2019Donnell, L. Mechanisms of spermiogenesis and spermiation and how they are disturbed. Spermatogenesis 4, e979623, https:\/\/doi.org\/10.4161\/21565562.2014.979623 (2014).","journal-title":"Spermatogenesis"},{"key":"25468_CR49","doi-asserted-by":"publisher","first-page":"14206","DOI":"10.1073\/pnas.212527899","volume":"99","author":"A Saiardi","year":"2002","unstructured":"Saiardi, A., Sciambi, C., McCaffery, J. M., Wendland, B. & Snyder, S. H. Inositol pyrophosphates regulate endocytic trafficking. Proc Natl Acad Sci USA 99, 14206\u201314211, https:\/\/doi.org\/10.1073\/pnas.212527899 (2002).","journal-title":"Proc Natl Acad Sci USA"},{"key":"25468_CR50","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1002\/dvg.20620","volume":"48","author":"M George","year":"2010","unstructured":"George, M. et al. Ehd4 is required to attain normal prepubertal testis size but dispensable for fertility in male mice. Genesis 48, 328\u2013342, https:\/\/doi.org\/10.1002\/dvg.20620 (2010).","journal-title":"Genesis"},{"key":"25468_CR51","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1016\/j.molmet.2016.08.008","volume":"5","author":"S Ghoshal","year":"2016","unstructured":"Ghoshal, S. et al. TNP [N2-(m-Trifluorobenzyl), N6-(p-nitrobenzyl)purine] ameliorates diet induced obesity and insulin resistance via inhibition of the IP6K1 pathway. Mol Metab 5, 903\u2013917, https:\/\/doi.org\/10.1016\/j.molmet.2016.08.008S2212-8778(16)30125-9 (2016).","journal-title":"Mol Metab"},{"key":"25468_CR52","doi-asserted-by":"crossref","first-page":"2885","DOI":"10.1242\/jeb.205.18.2885","volume":"205","author":"RL Ingermann","year":"2002","unstructured":"Ingermann, R. L., Holcomb, M., Robinson, M. L. & Cloud, J. G. Carbon dioxide and pH affect sperm motility of white sturgeon (Acipenser transmontanus). J Exp Biol 205, 2885\u20132890 (2002).","journal-title":"J Exp Biol"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-25468-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-25468-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-25468-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T04:54:38Z","timestamp":1671598478000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-25468-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5,4]]},"references-count":52,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["25468"],"URL":"https:\/\/doi.org\/10.1038\/s41598-018-25468-8","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,5,4]]},"assertion":[{"value":"2 January 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 April 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 May 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"7039"}}