{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:48:53Z","timestamp":1791978533663,"version":"4.4.0"},"reference-count":55,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T00:00:00Z","timestamp":1675123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["336450"],"award-info":[{"award-number":["336450"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["BB\/S01716X\/1"],"award-info":[{"award-number":["BB\/S01716X\/1"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["708051"],"award-info":[{"award-number":["708051"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Biotechnology and Biological Sciences Research Council","award":["336450"],"award-info":[{"award-number":["336450"]}]},{"name":"Biotechnology and Biological Sciences Research Council","award":["BB\/S01716X\/1"],"award-info":[{"award-number":["BB\/S01716X\/1"]}]},{"name":"Biotechnology and Biological Sciences Research Council","award":["708051"],"award-info":[{"award-number":["708051"]}]},{"name":"University of Leeds Scholarship","award":["336450"],"award-info":[{"award-number":["336450"]}]},{"name":"University of Leeds Scholarship","award":["BB\/S01716X\/1"],"award-info":[{"award-number":["BB\/S01716X\/1"]}]},{"name":"University of Leeds Scholarship","award":["708051"],"award-info":[{"award-number":["708051"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation programme","award":["336450"],"award-info":[{"award-number":["336450"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation programme","award":["BB\/S01716X\/1"],"award-info":[{"award-number":["BB\/S01716X\/1"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation programme","award":["708051"],"award-info":[{"award-number":["708051"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Deleterious mutations in the X-linked Patched domain-containing 1 (PTCHD1) gene may account for up to 1% of autism cases. Despite this, the PTCHD1 protein remains poorly understood. Structural similarities to Patched family proteins point to a role in sterol transport, but this hypothesis has not been verified experimentally. Additionally, PTCHD1 has been suggested to be involved in Hedgehog signalling, but thus far, the experimental results have been conflicting. To enable a variety of biochemical and structural experiments, we developed a method for expressing PTCHD1 in Spodoptera frugiperda cells, solubilising it in glycol-diosgenin, and purifying it to homogeneity. In vitro and in silico experiments show that PTCHD1 function is not interchangeable with Patched 1 (PTCH1) in canonical Hedgehog signalling, since it does not repress Smoothened in Ptch1\u2212\/\u2212 mouse embryonic fibroblasts and does not bind Sonic Hedgehog. However, we found that PTCHD1 binds cholesterol similarly to PTCH1. Furthermore, we identified 13 PTCHD1-specific protein interactors through co-immunoprecipitation and demonstrated a link to cell stress responses and RNA stress granule formation. Thus, our results support the notion that despite structural similarities to other Patched family proteins, PTCHD1 may have a distinct cellular function.<\/jats:p>","DOI":"10.3390\/ijms24032682","type":"journal-article","created":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T02:29:03Z","timestamp":1675218543000},"page":"2682","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["PTCHD1 Binds Cholesterol but Not Sonic Hedgehog, Suggesting a Distinct Cellular Function"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3773-4457","authenticated-orcid":false,"given":"Mimmu K.","family":"Hiltunen","sequence":"first","affiliation":[{"name":"Faculty of Biological and Environmental Sciences, University of Helsinki, 00100 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex J.","family":"Timmis","sequence":"additional","affiliation":[{"name":"School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maren","family":"Thomsen","sequence":"additional","affiliation":[{"name":"Astbury Center for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danai S.","family":"Gkotsi","sequence":"additional","affiliation":[{"name":"School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK"},{"name":"Astbury Center for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7376-5264","authenticated-orcid":false,"given":"Hideo","family":"Iwa\u00ef","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology, HiLiFE, University of Helsinki, 00100 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0746-6666","authenticated-orcid":false,"given":"Orquidea M.","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Faculty of Biological and Environmental Sciences, University of Helsinki, 00100 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Goldman","sequence":"additional","affiliation":[{"name":"Faculty of Biological and Environmental Sciences, University of Helsinki, 00100 Helsinki, Finland"},{"name":"Astbury Center for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8942-7873","authenticated-orcid":false,"given":"Natalia A.","family":"Riobo-Del Galdo","sequence":"additional","affiliation":[{"name":"School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK"},{"name":"Astbury Center for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK"},{"name":"Leeds Institute of Medical Research, University of Leeds, Leeds LS2 9JT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1016\/j.neuron.2011.05.021","article-title":"Rare de novo variants associated with autism implicate a large functional network of genes involved in formation and function of synapses","volume":"70","author":"Gilman","year":"2011","journal-title":"Neuron"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.ajhg.2012.12.016","article-title":"Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder","volume":"92","author":"Girirajan","year":"2013","journal-title":"Am. 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