{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T18:02:32Z","timestamp":1780336952311,"version":"3.54.1"},"reference-count":44,"publisher":"The Company of Biologists","issue":"21","license":[{"start":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T00:00:00Z","timestamp":1698796800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"funder":[{"DOI":"10.13039\/501100004541","name":"Ministry of Education, Government of India","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004541","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001843","name":"Science and Engineering Research Board","doi-asserted-by":"crossref","award":["ECR\/2017\/001410"],"award-info":[{"award-number":["ECR\/2017\/001410"]}],"id":[{"id":"10.13039\/501100001843","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Department of Biotechnology","award":["BT\/12\/IYBA\/2019\/02"],"award-info":[{"award-number":["BT\/12\/IYBA\/2019\/02"]}]},{"DOI":"10.13039\/501100006593","name":"Board of Research in Nuclear Sciences","doi-asserted-by":"crossref","award":["55\/14\/02\/2021-BRNS\/10206"],"award-info":[{"award-number":["55\/14\/02\/2021-BRNS\/10206"]}],"id":[{"id":"10.13039\/501100006593","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,11,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Centrioles are microtubule-based cylindrical ultrastructures characterized by their definite size and robustness. The molecular capping protein, CPAP (also known as CENPJ) engages its N-terminal region with the centriole microtubules to regulate their length. Nevertheless, the conserved C-terminal glycine-rich G-box of CPAP, which interacts with the centriole inner cartwheel protein STIL, is frequently mutated in primary microcephaly (MCPH) patients. Here, we show that two different MCPH-associated variants, E1235V and D1196N in the CPAP G-box, affect distinct functions at centrioles. The E1235V mutation reduces CPAP centriole recruitment and causes overly long centrioles. The D1196N mutation increases centriole numbers without affecting centriole localization. Both mutations prevent binding to STIL, which controls centriole duplication. Our work highlights the involvement of an alternative CEP152-dependent route for CPAP centriole localization. Molecular dynamics simulations suggest that E1235V leads to an increase in G-box flexibility, which could have implications on its molecular interactions. Collectively, we demonstrate that a CPAP region outside the microtubule-interacting domains influences centriole number and length, which translates to spindle defects and reduced cell viability. Our work provides new insights into the molecular causes of primary microcephaly.<\/jats:p>","DOI":"10.1242\/jcs.261297","type":"journal-article","created":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T09:25:09Z","timestamp":1697102709000},"source":"Crossref","is-referenced-by-count":6,"title":["Separation-of-function MCPH-associated mutations in CPAP affect centriole number and length"],"prefix":"10.1242","volume":"136","author":[{"given":"Sonal","family":"Jaiswal","sequence":"first","affiliation":[{"name":"Indian Institute of Technology Jodhpur Department of Bioscience & Bioengineering , , NH 62, Nagaur Road, Karwar 342037, Jodhpur, Rajasthan , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srishti","family":"Sanghi","sequence":"additional","affiliation":[{"name":"Indian Institute of Technology Jodhpur Department of Bioscience & Bioengineering , , NH 62, Nagaur Road, Karwar 342037, Jodhpur, Rajasthan , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5928-6280","authenticated-orcid":false,"given":"Priyanka","family":"Singh","sequence":"additional","affiliation":[{"name":"Indian Institute of Technology Jodhpur Department of Bioscience & Bioengineering , , NH 62, Nagaur Road, Karwar 342037, Jodhpur, Rajasthan , India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2023,11,6]]},"reference":[{"key":"2023110611061658800_JCS261297C1","doi-asserted-by":"publisher","first-page":"830432","DOI":"10.3389\/fcell.2022.830432","article-title":"Modeling human primary microcephaly with hiPSC-derived brain organoids carrying CPAP-E1235V disease-associated mutant protein","volume":"10","author":"An","year":"2022","journal-title":"Front. 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