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The human pathogen\n                    <jats:italic>Cryptococcus neoformans<\/jats:italic>\n                    possesses a unique\n                    <jats:italic>N<\/jats:italic>\n                    -glycosylation pathway that affects microbial physiology and interactions with the infected host. To investigate the molecular features and functions of the ERQC system in\n                    <jats:italic>C. neoformans,<\/jats:italic>\n                    we characterized a set of mutants with deletion of genes coding for the ERQC sensor UDP-glucose:glycoprotein glucosyltransferase (\n                    <jats:italic>UGG1<\/jats:italic>\n                    ) and putative \u03b11,2-mannose-trimming enzymes (\n                    <jats:italic>MNS1<\/jats:italic>\n                    ,\n                    <jats:italic>MNS101<\/jats:italic>\n                    ,\n                    <jats:italic>MNL1<\/jats:italic>\n                    , and\n                    <jats:italic>MNL2<\/jats:italic>\n                    ). The\n                    <jats:italic>ugg1<\/jats:italic>\n                    \u0394,\n                    <jats:italic>mns1<\/jats:italic>\n                    \u0394,\n                    <jats:italic>mns101<\/jats:italic>\n                    \u0394, and\n                    <jats:italic>mns1<\/jats:italic>\n                    \u0394\n                    <jats:italic>101<\/jats:italic>\n                    \u0394 mutants showed alterations in\n                    <jats:italic>N<\/jats:italic>\n                    -glycan profiles, defective cell surface organization, decreased survival in host cells, and varying degrees of reduced\n                    <jats:italic>in vivo<\/jats:italic>\n                    virulence. The\n                    <jats:italic>ugg1<\/jats:italic>\n                    \u0394 strain exhibited severely impaired extracellular secretion of capsular polysaccharides and virulence-related enzymes. Comparative transcriptome analysis showed the upregulation of protein folding, proteolysis, and cell wall remodeling genes, indicative of induced endoplasmic reticulum stress. However, no apparent changes were observed in the expression of genes involved in protein secretion or capsule biosynthesis. Additionally, extracellular vesicle (EV) analysis combined with proteomic analysis showed significant alterations in the number, size distribution, and cargo composition of EVs in\n                    <jats:italic>ugg1<\/jats:italic>\n                    \u0394. These findings highlight the essential role of the functional ERQC system for cellular fitness under adverse conditions and proper EV-mediated transport of virulence factors, which are crucial for the full fungal pathogenicity of\n                    <jats:italic>C. neoformans<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.7554\/elife.103729","type":"journal-article","created":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T13:25:09Z","timestamp":1733145909000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.103729","source":"Crossref","is-referenced-by-count":3,"title":["Evolutionary unique N-glycan-dependent protein quality control system plays pivotal roles in cellular fitness and extracellular vesicle transport in Cryptococcus neoformans"],"prefix":"10.7554","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-6129-0000","authenticated-orcid":true,"given":"Catia","family":"Mota","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01r024a98","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Life Science, Chung-Ang University","place":["Seoul, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8602-3293","authenticated-orcid":true,"given":"Kiseung","family":"Kim","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01r024a98","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Life Science, Chung-Ang University","place":["Seoul, Republic of 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