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It is caused by mutations in the oculocerebrorenal syndrome of Lowe (OCRL) protein, a 5\u2010phosphatase localised in different cellular compartments that dephosphorylates phosphatidylinositol\u20104,5\u2010bisphosphate into phosphatidylinositol\u20104\u2010monophosphate. Some patients with LS also have bleeding disorders, with normal to low platelet (PLT) count and impaired PLT function. However, the mechanism of PLT dysfunction in patients with LS is not completely understood. The main function of PLTs is to activate upon vessel wall injury and stop the bleeding by clot formation. PLT activation is accompanied by a shape change that is a result of massive cytoskeletal rearrangements. Here, we show that OCRL\u2010inhibited human PLTs do not fully spread, form mostly filopodia, and accumulate actin nodules. These nodules co\u2010localise with ARP2\/3 subunit p34, vinculin, and sorting nexin 9. Furthermore, OCRL\u2010inhibited PLTs have a retained microtubular coil with high levels of acetylated tubulin. Also, myosin light chain phosphorylation is decreased upon OCRL inhibition, without impaired degranulation or integrin activation. Taken together, these results suggest that OCRL contributes to cytoskeletal rearrangements during PLT activation that could explain mild bleeding problems in patients with LS.<\/jats:p>","DOI":"10.1111\/bjh.18478","type":"journal-article","created":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T06:14:54Z","timestamp":1664518494000},"page":"87-99","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Oculocerebrorenal syndrome of Lowe protein controls cytoskeletal reorganisation during human platelet spreading"],"prefix":"10.1111","volume":"200","author":[{"given":"Ana","family":"Bura","sequence":"first","affiliation":[{"name":"Department of Biotechnology University of Rijeka  Rijeka Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Antonietta","family":"de Matteis","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine, TIGEM  Pozzuoli Naples Italy"},{"name":"Department of Molecular Medicine and Medical Biotechnology University of Naples Federico II  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2381-116X","authenticated-orcid":false,"given":"Markus","family":"Bender","sequence":"additional","affiliation":[{"name":"Institute of Experimental Biomedicine University Hospital Wuerzburg, Rudolf Virchow Center  Wuerzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6667-9031","authenticated-orcid":false,"given":"Maurice","family":"Swinkels","sequence":"additional","affiliation":[{"name":"Erasmus MC University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jurjen","family":"Versluis","sequence":"additional","affiliation":[{"name":"Erasmus MC University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2612-1420","authenticated-orcid":false,"given":"A. 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