{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T21:57:23Z","timestamp":1787003843212,"version":"build-2736575974"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2015,12,16]],"date-time":"2015-12-16T00:00:00Z","timestamp":1450224000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2015,12,16]],"date-time":"2015-12-16T00:00:00Z","timestamp":1450224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Mutations in\n                    <jats:italic>protein kinase C substrate 80K-H (PRKCSH)<\/jats:italic>\n                    , which encodes for an 80\u2009KDa protein named hepatocystin (80K-H,\n                    <jats:italic>PRKCSH<\/jats:italic>\n                    ), gives rise to polycystic liver disease (PCLD). Hepatocystin functions as the noncatalytic beta subunit of Glucosidase II, an endoplasmic reticulum (ER)-resident enzyme involved in processing and quality control of newly synthesized glycoproteins. Patients harboring heterozygous germline mutations in\n                    <jats:italic>PRKCSH<\/jats:italic>\n                    are thought to develop renal cysts as a result of somatic loss of the second allele, which subsequently interferes with expression of the TRP channel polycystin-2 (PKD2). Deletion of both alleles of\n                    <jats:italic>PRKCSH<\/jats:italic>\n                    in mice results in embryonic lethality before embryonic day E11.5. Here, we investigated the function of hepatocystin during\n                    <jats:italic>Xenopus laevis<\/jats:italic>\n                    embryogenesis and identified hepatocystin as a binding partner of the TRPM7 ion channel, whose function is required for vertebrate gastrulation. We find that TRPM7 functions synergistically with hepatocystin. Although other N-glycosylated proteins are critical to early development, overexpression of TRPM7 in\n                    <jats:italic>Xenopus laevis<\/jats:italic>\n                    embryos was sufficient to fully rescue the gastrulation defect caused by loss of hepatocystin. We observed that depletion of hepatocystin in\n                    <jats:italic>Xenopus<\/jats:italic>\n                    laevis embryos decreased TRPM7 expression, indicating that the early embryonic lethality caused by loss of hepatocystin is mainly due to impairment of TRPM7 protein expression.\n                  <\/jats:p>","DOI":"10.1038\/srep18395","type":"journal-article","created":{"date-parts":[[2015,12,16]],"date-time":"2015-12-16T05:17:28Z","timestamp":1450243048000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Hepatocystin is Essential for TRPM7 Function During Early Embryogenesis"],"prefix":"10.1038","volume":"5","author":[{"given":"Jeffrey D.","family":"Overton","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Komiya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney","family":"Mezzacappa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaushik","family":"Nama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Lou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sorin V.","family":"Fedeles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond","family":"Habas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loren W.","family":"Runnels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,12,16]]},"reference":[{"key":"BFsrep18395_CR1","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1085\/jgp.20028740","volume":"121","author":"MK Monteilh-Zoller","year":"2003","unstructured":"Monteilh-Zoller, M. K. et al. TRPM7 provides an ion channel mechanism for cellular entry of trace metal ions. J Gen Physiol 121, 49\u201360 (2003).","journal-title":"J Gen Physiol"},{"key":"BFsrep18395_CR2","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1038\/35079092","volume":"411","author":"MJ Nadler","year":"2001","unstructured":"Nadler, M. J. et al. LTRPC7 is a Mg.ATP-regulated divalent cation channel required for cell viability. Nature 411, 590\u2013595 (2001).","journal-title":"Nature"},{"key":"BFsrep18395_CR3","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1126\/science.1058519","volume":"291","author":"LW Runnels","year":"2001","unstructured":"Runnels, L. W., Yue, L. & Clapham, D. E. TRP-PLIK, a bifunctional protein with kinase and ion channel activities. Science 291, 1043\u20131047 (2001).","journal-title":"Science"},{"key":"BFsrep18395_CR4","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1126\/science.1163493","volume":"322","author":"J Jin","year":"2008","unstructured":"Jin, J. et al. Deletion of Trpm7 disrupts embryonic development and thymopoiesis without altering Mg2+ homeostasis. Science 322, 756\u2013760 (2008).","journal-title":"Science"},{"key":"BFsrep18395_CR5","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1016\/j.ydbio.2010.11.034","volume":"350","author":"W Liu","year":"2011","unstructured":"Liu, W. et al. TRPM7 regulates gastrulation during vertebrate embryogenesis. Developmental biology 350, 348\u2013357 (2011).","journal-title":"Developmental biology"},{"key":"BFsrep18395_CR6","first-page":"9990","volume":"257","author":"DM Burns","year":"1982","unstructured":"Burns, D. M. & Touster, O. 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