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In the model yeast\n              <jats:italic>Saccharomyces cerevisiae<\/jats:italic>\n              ,\n              <jats:italic>Sc<\/jats:italic>\n              Glc7p and\n              <jats:italic>Sc<\/jats:italic>\n              Gac1p are the serine\/threonine type 1 protein phosphatase catalytic and regulatory subunits that control glycogen synthesis by altering the phosphorylation state of the glycogen synthase Gsy2p. Despite recent delineation of the glycogen synthesis pathway in\n              <jats:italic>C. albicans<\/jats:italic>\n              , the molecular events driving synthase activation are currently undefined. In this study, using a combination of microbiologic and genetic techniques, we determined that the protein encoded by uncharacterized gene\n              <jats:italic>C1_01140C<\/jats:italic>\n              , and not the currently annotated\n              <jats:italic>C. albicans<\/jats:italic>\n              Gac1p, is the major regulatory subunit involved in glycogen synthesis. C1_01140Cp contains a conserved GVNK motif observed across multiple starch\/glycogen-binding proteins in various species, and alanine substitution of each residue in this motif significantly impaired glycogen accumulation in\n              <jats:italic>C. albicans<\/jats:italic>\n              . Fluorescent protein tagging and microscopy indicated that C1_01140Cp-GFPy colocalized with\n              <jats:italic>Ca<\/jats:italic>\n              Glc7p-tdTomato and\n              <jats:italic>Ca<\/jats:italic>\n              Gsy1p-tdTomato accordingly. Co-immunoprecipitation assays further confirmed that C1_01140Cp associates with\n              <jats:italic>Ca<\/jats:italic>\n              Glc7p and\n              <jats:italic>Ca<\/jats:italic>\n              Gsy1p during glycogen synthesis. Lastly,\n              <jats:italic>c1_01140c<\/jats:italic>\n              \u0394\/\u0394 exhibited colonization defects in a murine model of vulvovaginal candidiasis. Collectively, our data indicate that uncharacterized C1_01140Cp is the functional ortholog of the PPP1R subunit\n              <jats:italic>Sc<\/jats:italic>\n              Gac1p in\n              <jats:italic>C. albicans<\/jats:italic>\n              .\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>\n                The capacity to synthesize glycogen offers microbes metabolic flexibility, including the fungal pathogen\n                <jats:italic>Candida albicans<\/jats:italic>\n                . In\n                <jats:italic>Saccharomyces cerevisiae<\/jats:italic>\n                , dephosphorylation of glycogen synthase by the\n                <jats:italic>Sc<\/jats:italic>\n                Glc7p-containing phosphatase is a critical rate-limiting step in glycogen synthesis. Subunits, including\n                <jats:italic>Sc<\/jats:italic>\n                Gac1p, target\n                <jats:italic>Sc<\/jats:italic>\n                Glc7p to \u03b1-1,4-glucosyl primers for efficient\n                <jats:italic>Sc<\/jats:italic>\n                Gsy2p synthase activation. However, this process in\n                <jats:italic>C. albicans<\/jats:italic>\n                had not been delineated. Here, we show that the\n                <jats:italic>C. albicans<\/jats:italic>\n                genome encodes for two homologous phosphatase-binding subunits, annotated\n                <jats:italic>Ca<\/jats:italic>\n                Gac1p and uncharacterized C1_01140Cp, both containing a GVNK motif required for polysaccharide affinity. Surprisingly, loss of\n                <jats:italic>Ca<\/jats:italic>\n                Gac1p only moderately reduced glycogen accumulation, whereas loss of C1_01140Cp ablated it. Fluorescence microscopy and co-immunoprecipitation approaches revealed that C1_01140Cp associates with\n                <jats:italic>Ca<\/jats:italic>\n                Glc7p and\n                <jats:italic>Ca<\/jats:italic>\n                Gsy1p during glycogen synthesis. Moreover, C1_01140Cp contributed to fungal fitness at the vaginal mucosa during murine vaginitis. Therefore, this work demonstrates that glycogen synthase regulation is conserved in\n                <jats:italic>C. albicans<\/jats:italic>\n                and C1_01140Cp is the functional ortholog of\n                <jats:italic>Sc<\/jats:italic>\n                Gac1p.\n              <\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/msphere.00575-24","type":"journal-article","created":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T13:05:50Z","timestamp":1727183150000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["Glycogen synthase activity in\n            <i>Candida albicans<\/i>\n            is partly controlled by the functional ortholog of\n            <i>Saccharomyces cerevisiae<\/i>\n            Gac1p"],"prefix":"10.1128","volume":"9","author":[{"given":"Jian","family":"Miao","sequence":"first","affiliation":[{"name":"Pharmaceutical Sciences Program, College of 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