{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T10:38:29Z","timestamp":1791110309986,"version":"4.1.0"},"reference-count":43,"publisher":"National Academy of Sciences","issue":"12","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2005,3,22]]},"abstract":"<jats:p>\n                    Neutral sphingomyelinases sphingomyelin phosphodiesterase (SMPD)2 and -3 hydrolyze sphingomyelin to phosphocholine and ceramide.\n                    <jats:italic>smpd2<\/jats:italic>\n                    is expressed ubiquitously, and\n                    <jats:italic>smpd3<\/jats:italic>\n                    is expressed predominantly in neurons of the CNS. Their activation and the functions of the released ceramides have been associated with signaling pathways in cell growth, differentiation, and apoptosis. However, these cellular responses remain poorly understood. Here we describe the generation and characterization of the\n                    <jats:italic>smpd3<\/jats:italic>\n                    <jats:sup>\n                      \u2013\n                      <jats:italic>\/<\/jats:italic>\n                      \u2013\n                    <\/jats:sup>\n                    and\n                    <jats:italic>smpd2<\/jats:italic>\n                    <jats:sup>\n                      \u2013\n                      <jats:italic>\/<\/jats:italic>\n                      \u2013\n                    <\/jats:sup>\n                    <jats:italic>smpd3<\/jats:italic>\n                    <jats:sup>\n                      \u2013\n                      <jats:italic>\/<\/jats:italic>\n                      \u2013\n                    <\/jats:sup>\n                    double mutant mouse, which proved to be devoid of neutral sphingomyelinase activity. SMPD3 plays a pivotal role in the control of late embryonic and postnatal development: the\n                    <jats:italic>smpd3<\/jats:italic>\n                    -null mouse develops a novel form of dwarfism and delayed puberty as part of a hypothalamus-induced combined pituitary hormone deficiency. Our studies suggest that SMPD3 is segregated into detergent-resistant subdomains of Golgi membranes of hypothalamic neurosecretory neurons, where its transient activation modifies the lipid bilayer, an essential step in the Golgi secretory pathway. The\n                    <jats:italic>smpd3<\/jats:italic>\n                    <jats:sup>\n                      \u2013\n                      <jats:italic>\/<\/jats:italic>\n                      \u2013\n                    <\/jats:sup>\n                    mouse might mimic a form of human combined pituitary hormone deficiency.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0406380102","type":"journal-article","created":{"date-parts":[[2005,3,11]],"date-time":"2005-03-11T20:24:50Z","timestamp":1110572690000},"page":"4554-4559","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":156,"title":["Neutral sphingomyelinase 2 (\n                    <i>smpd3<\/i>\n                    ) in the control of postnatal growth and development"],"prefix":"10.1073","volume":"102","author":[{"given":"Wilhelm","family":"Stoffel","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Neurosciences, Center of Molecular Medicine, Center of Biochemistry, and Center of Anatomy, Faculty of Medicine, University of Cologne, D-50931 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Britta","family":"Jenke","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neurosciences, Center of Molecular Medicine, Center of Biochemistry, and Center of Anatomy, Faculty of Medicine, University of Cologne, D-50931 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Bl\u00f6ck","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neurosciences, Center of Molecular Medicine, Center of Biochemistry, and Center of Anatomy, Faculty of Medicine, University of Cologne, D-50931 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Zumbansen","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neurosciences, Center of Molecular Medicine, Center of Biochemistry, and Center of Anatomy, Faculty of Medicine, University of Cologne, D-50931 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Koebke","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neurosciences, Center of Molecular Medicine, Center of Biochemistry, and Center of Anatomy, Faculty of Medicine, University of Cologne, D-50931 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2005,3,11]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)96805-5"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)99833-9"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2760(87)90055-5"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1989.tb08382.x"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1515\/bchm3.1992.373.2.1233"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.50.32089"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(05)80010-8"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0795-288"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1978.tb10804.x"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.60.1.643"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R200008200"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(98)01289-4"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.11.3633-3638.2002"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.7.3638"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.8.5710"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.11.5895"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/347528a0"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/384327a0"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.257.5073.1115"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.13.6646"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.162352599"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(00)00152-4"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.151.1.143"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1139\/y59-099"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.16.10904"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1210\/edrv-10-1-68"},{"key":"e_1_3_2_27_2","first-page":"311","volume":"73","year":"1995","unstructured":"Rubin, R. & Baserga, R. 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