Essential role of the nucleotide-sugar transporter Slc35d1 in intestinal homeostasis

• Project/Area Number: 25670170
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pathological medical chemistry
• Research Institution: Kobe Pharmaceutical University
• Principal Investigator: SHUICHI Hiraoka 神戸薬科大学, 薬学部, 研究員 (20291156)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 糖ヌクレオチド輸送体 / 腸管機能 / ホメオスタシス / コンドロイチン硫酸 / 腸管 / 腸管ホメオスタシス / グリコサミノグリカン

Outline of Final Research Achievements

The nucleotide-sugar transporter Slc35d1 transports the substrates for chondroitin sulfate (CS) and heparan sulfate from cytosol into lumens of Golgi apparatus and ER. To investigate in vivo role of the Slc35d1, we generated Slc35d1flox-Rosa CreERT mice (Slc35d1-iKO mouse), of which Slc35d1 gene could be artificially disrupted by the administration of tamoxifen (TXF). The Slc35d1-iKO mouse was dead within 10 days by the TXF administration, suffering from diarrhea. We observed the intestinal villous atrophy and 30% reduction of CS prior to morphological affection of villi. Based on these observations, we concluded that the Slc35d1 is required for intestinal homeostasis. It is likely that reduction of the CS in the Slc35d1-iKO mouse induced villous atrophy leading to lethal malnutrition.

Research Products

• [Journal Article] CCN3 protein participates in bone regeneration as an inhibitory factor. (2013)
  • Author(s): Matsushita Y, Sakamoto K, Tamamura Y, Shibata Y, Minamizato T, Kihara T, Ito M, Katsube K, Hiraoka S, Koseki H, Harada K, Yamaguchi A.
  • Journal Title: The Journal of Biological Chemistry Volume: 288 Issue: 27 Pages: 19973-19985
  • DOI: 10.1074/jbc.m113.454652
  • Peer Reviewed
• [Presentation] 糖ヌクレオチド輸送体Slc35d1は腸管ホメオスタシスに必要である (2014)
  • Author(s): 平岡秀一、古関明彦、北川裕之
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-11-25