The HNF-1 target Collectrin controls insulin exocytosis by SNARE complex formation

Fukui, Kenji; Yang, Qin; Cao, Yang; Takahashi, Noriko; Hatakeyama, Hiroyasu; Wang, Haiyan; Wada, Jun; Zhang, Yanling; Marselli, Lorella; Nammo, Takao; Yoneda, Kazue; Onishi, Masanori; Higashiyama, Shigeki; Matsuzawa, Yūji; Gonzalez, Frank J.; Weir, Gordon C.; Kasai, Hideaki; Shimomura, Iichiro; Miyagawa, Jun Ichiro; Wollheim, Claes B.; Yamagata, Kazuya

doi:10.1016/j.cmet.2005.11.003

Cited by 142 publications

(148 citation statements)

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“…This is consistent with the observed role of glutamine in the release of insulin from pancreatic ␤-cells (38). We could detect B 0 AT1 mRNA in pancreas but do not know whether it is expressed in ␤-cells, where the B 0 AT1 trafficking subunit collectrin has been found (39,40). It has been reported that some strains of C57Bl/6J mice have deletions in the nicotinamide nucleotide transhydrogenase (Nnt), resulting in a reduced insulin response (17).…”

Section: Discussionsupporting

confidence: 73%

Impaired Nutrient Signaling and Body Weight Control in a Na+ Neutral Amino Acid Cotransporter (Slc6a19)-deficient Mouse

Bröer

Juelich

Vanslambrouck

et al. 2011

Journal of Biological Chemistry

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Amino acid uptake in the intestine and kidney is mediated by a variety of amino acid transporters. To understand the role of epithelial neutral amino acid uptake in whole body homeostasis, we analyzed mice lacking the apical broad-spectrum neutral (0) amino acid transporter B 0 AT1 (Slc6a19). A general neutral aminoaciduria was observed similar to human Hartnup disorder which is caused by mutations in SLC6A19. Na ؉ -dependent uptake of neutral amino acids into the intestine and renal brushborder membrane vesicles was abolished. No compensatory increase of peptide transport or other neutral amino acid transporters was detected. Mice lacking B 0 AT1 showed a reduced body weight. When adapted to a standard 20% protein diet, B 0 AT1-deficient mice lost body weight rapidly on diets containing 6 or 40% protein. Secretion of insulin in response to food ingestion after fasting was blunted. In the intestine, amino acid signaling to the mammalian target of rapamycin (mTOR) pathway was reduced, whereas the GCN2/ATF4 stress response pathway was activated, indicating amino acid deprivation in epithelial cells. The results demonstrate that epithelial amino acid uptake is essential for optimal growth and body weight regulation.In a typical Western diet humans consume about 80 -100 g of protein per day. Proteins are hydrolyzed by the action of secreted and membrane-bound peptidases into individual amino acids, di-and tripeptides (1). Individual amino acids are taken up by a variety of amino acid transporters, whereas diand tripeptides are absorbed by the peptide transporter PepT1 (SLC15A1) (2). Together this digestive process makes 90 -95% of ingested proteins available to the body. Protein demand is particularly high during growth and development when new proteins are required to build up body mass. In the adult, protein recycling is quite efficient, and only 50 g of protein is needed per day to replace protein lost through urine and feces.The bulk of neutral amino acids is absorbed in the intestine by the neutral amino acid transporter B 0 AT1 (SLC6A19), which is also expressed in the kidney where it mediates reabsorption of neutral amino acids (3). Expression studies in heterologous systems have shown that B 0 AT1 accepts all neutral amino acids with a preference for large neutral amino acids such as branched-chain amino acids and methionine (4, 5). These amino acids are taken up with a K m of about 1 mM, whereas smaller amino acids are taken up with higher K m values. Glycine and proline are poor substrates of B 0 AT1. As a result additional transporters are involved in the uptake of imino acids and glycine, such as PAT1 (SLC36A1), PAT2 (SLC36A2), and IMINO (SLC6A20) (6). Additional transport systems for other neutral amino acids in the kidney and intestine have been proposed; these include a specific intestinal transporter for methionine and phenylalanine (7) and the amino acid antiporter ASCT2 (SLC1A5) as a mediator of small neutral amino acids and glutamine uptake in kidney and intestine (8).Efficient trafficking and sur...

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Section: Discussionsupporting

confidence: 73%

Impaired Nutrient Signaling and Body Weight Control in a Na+ Neutral Amino Acid Cotransporter (Slc6a19)-deficient Mouse

Bröer

Juelich

Vanslambrouck

et al. 2011

Journal of Biological Chemistry

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“…LCM was performed as previously described [30]. Frozen pancreatic Quantitative measurements of specific transcripts were acquired by real-time RT-PCR.…”

Section: Methodsmentioning

confidence: 99%

The endoplasmic reticulum in pancreatic beta cells of type 2 diabetes patients

et al. 2007

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Aims/hypothesis Pancreatic beta cells have highly developed endoplasmic reticulum (ER) due to their role in insulin secretion. Since ER stress has been associated with beta cell dysfunction, we studied several features of beta cell ER in human type 2 diabetes. Methods Pancreatic samples and/or isolated islets from non-diabetic controls (ND) and type 2 diabetes patients were evaluated for insulin secretion, apoptosis (electron microscopy and ELISA), morphometric ER assessment (electron microscopy), and expression of ER stress markers in beta cell prepared by laser capture microdissection and in isolated islets.Results Insulin release was lower and beta cell apoptosis higher in type 2 diabetes than ND islets. ER density volume was significantly increased in type 2 diabetes beta cells. Expression of alpha-mannosidase (also known as mannosidase, alpha, class 1A, member 1) and UDP-glucose glycoprotein glucosyl transferase like 2 (UGCGL2), assessed by microarray and/or real-time reverse transcriptase polymerase chain reaction (RT-PCR), differed between ND and type 2 diabetes beta cells. Expression of immunoglobulin heavy chain binding protein (BiP, also known as heat shock 70 kDa protein 5 [glucose-regulated protein, 78 kDa] [HSPA5]), X-box binding protein 1 (XBP-1, also known as XBP1) and C/EBP homologous protein (CHOP, also known as damage-inducible transcript 3 [DDIT3]) was not higher in type 2 diabetes beta cell or isolated islets cultured at 5.5 mmol/l glucose (microarray and real-time RT-PCR) than in ND samples. When islets were cultured for 24 h at 11

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“…The C-terminal domain of Tmem27 appears to be involved implication in glucose-stimulated insulin exocytosis and and/or ß-cell mass in pancreas, 67,68 as well as renal collecting duct primary cilium formation and polycystic kidney disease. 70 As described more in detail in later paragraphs, Tmem27 has also been shown to be critical for the correct expression of amino acid transporters in kidney.…”

Section: 11mentioning

confidence: 99%

“…65 Tmem27 has been shown to be expressed in liver, lung, endocrine pancreas and kidney proximal tubule brush border membrane and collecting duct, hence the misleading name Collectrin. 12,13,67,68 Given the lack of Tmem27 catalytic activity, it does not seem to play a role in the classical RAS although an implication in the development of salt sensitive hypertension has been suggested. 69 Tmem27 has been shown to bind proteins involved in intracellular and membrane protein trafficking and ciliary movement such as γ-actin-myosin II-A, snapin, SNAP-25 and polycystin-2-polaris complexes.…”

mentioning

confidence: 99%

Collectrin and ACE2 in renal and intestinal amino acid transport

Singer¹,

Camargo²

2011

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Neutral amino acid transporters of the SLC6 family are expressed at the apical membrane of kidney and/or small intestine, where they (re-)absorb amino acids into the body. In this review we present the results concerning the dependence of their apical expression on their association to partner proteins. We will in particular focus on the situation of B(0)AT1 and B(0)AT3, which associate with members of the renin-angiotensin system (RAS), namely Tmem27 and angiotensin-converting enzyme 2 (ACE2), in a tissue specific manner. The role of this association in relation to the formation of a functional unit related to Na(+) or amino acid transport will be assessed. We will conclude with some remarks concerning the relevance of this association to Hartnup disorder, where some mutations have been shown to differentially interact with the partner proteins

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The HNF-1 target Collectrin controls insulin exocytosis by SNARE complex formation

Cited by 142 publications

References 41 publications

Impaired Nutrient Signaling and Body Weight Control in a Na+ Neutral Amino Acid Cotransporter (Slc6a19)-deficient Mouse

Impaired Nutrient Signaling and Body Weight Control in a Na+ Neutral Amino Acid Cotransporter (Slc6a19)-deficient Mouse

The endoplasmic reticulum in pancreatic beta cells of type 2 diabetes patients

Collectrin and ACE2 in renal and intestinal amino acid transport

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