PMID- 19664597 OWN - NLM STAT- MEDLINE DCOM- 20090921 LR - 20201209 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 388 IP - 2 DP - 2009 Oct 16 TI - Identification of NPC2 protein as interaction molecule with C2 domain of human Nedd4L. PG - 290-6 LID - 10.1016/j.bbrc.2009.07.158 [doi] AB - Epithelial sodium channels (ENaC) located along the aldosterone-sensitive distal nephron (ASDN) play a pivotal role in the homeostasis of sodium balance. Among various modulating proteins, E3 ubiquitin ligase, Nedd4L, binds the PY motif of ENaC COOH terminals and catalyzes ubiquitination of the NH(2) terminal of the protein for subsequent degradation. One of the isoforms of human Nedd4L with evolutionarily new C2 domain was reported to play a significant role for degradating cell surface ENaC with interfering with wild isoforms by us previously. We focused the current analyses on isolating the binding molecules with C2 domain using yeast two-hybrid screening to elucidate further molecular interactions between ENaC and Nedd4L. We found NPC2, also known as HE-1, bind C2 domain of human Nedd4L and express along ASDN colocalized with Nedd4L. Additionally, in experiments using a model of salt-sensitive hypertension in Dahl rats, we provided evidence suggesting that transcriptional regulation and activation of NPC2 protein depends on sodium intake. NPC2 might regulate sodium reabsorption in the terminal nephron by interacting with ENaC-Nedd4L system. FAU - Araki, Naomi AU - Araki N AD - Yokohama City University Graduate School of Medicine, Department of Medical Science and Cardio-renal Medicine, Yokohama-city, Kanagawa-ken 236-0004, Japan. FAU - Ishigami, Tomoaki AU - Ishigami T FAU - Ushio, Hisako AU - Ushio H FAU - Minegishi, Shintaro AU - Minegishi S FAU - Umemura, Masanari AU - Umemura M FAU - Miyagi, Yohei AU - Miyagi Y FAU - Aoki, Ichiro AU - Aoki I FAU - Morinaga, Hiroko AU - Morinaga H FAU - Tamura, Koichi AU - Tamura K FAU - Toya, Yoshiyuki AU - Toya Y FAU - Uchino, Kazuaki AU - Uchino K FAU - Umemura, Satoshi AU - Umemura S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090805 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Carrier Proteins) RN - 0 (Endosomal Sorting Complexes Required for Transport) RN - 0 (Glycoproteins) RN - 0 (NPC2 protein, human) RN - 0 (Vesicular Transport Proteins) RN - 9NEZ333N27 (Sodium) RN - EC 2.3.2.26 (NEDD4L protein, rat) RN - EC 2.3.2.26 (Nedd4 Ubiquitin Protein Ligases) RN - EC 2.3.2.26 (Nedd4L protein, human) RN - EC 2.3.2.27 (Ubiquitin-Protein Ligases) SB - IM MH - Animals MH - Carrier Proteins/genetics/*metabolism MH - Endosomal Sorting Complexes Required for Transport MH - Gene Expression Regulation MH - Glycoproteins/genetics/*metabolism MH - Humans MH - Ion Transport MH - Nedd4 Ubiquitin Protein Ligases MH - Nephrons/*metabolism MH - Protein Structure, Tertiary MH - Rats MH - Rats, Inbred Dahl MH - Sodium/metabolism MH - Transcription, Genetic MH - Two-Hybrid System Techniques MH - Ubiquitin-Protein Ligases/genetics/*metabolism MH - Urothelium/metabolism MH - Vesicular Transport Proteins EDAT- 2009/08/12 09:00 MHDA- 2009/09/22 06:00 CRDT- 2009/08/12 09:00 PHST- 2009/07/28 00:00 [received] PHST- 2009/07/30 00:00 [accepted] PHST- 2009/08/12 09:00 [entrez] PHST- 2009/08/12 09:00 [pubmed] PHST- 2009/09/22 06:00 [medline] AID - S0006-291X(09)01549-6 [pii] AID - 10.1016/j.bbrc.2009.07.158 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2009 Oct 16;388(2):290-6. doi: 10.1016/j.bbrc.2009.07.158. Epub 2009 Aug 5.