Receptor-Mediated Transcytosis of Leptin through Human Intestinal Cells In Vitro.
Gastric Leptin is absorbed by duodenal enterocytes and released on the basolateral side towards the bloodstream. We investigated in vitro some of the mechanisms of this transport. Caco-2/15 cells internalize leptin from the apical medium and release it through transcytosis in the basal medium in a time- temperature-dependent and saturable fashion. Leptin receptors are revealed on the apical brush-border membrane of the Caco-2 cells. RNA-mediated silencing of the receptor led to decreases in the uptake and basolateral release. Leptin in the basal medium was found bound to the soluble form of its receptor. An inhibitor of clathrin-dependent endocytosis (chlorpromazine) decreased leptin uptake. Confocal immunocytochemistry and the use of brefeldin A and okadaic acid revealed the passage of leptin through the Golgi apparatus. We propose that leptin transcytosis by intestinal cells depends on its receptor, on clathrin-coated vesicles and transits through the Golgi apparatus.
Cammisotto
Philippe G
PG
Departments of Pathology and Cell Biology, University of Montreal, 2900, Bd Edouard-Montpetit, Montreal, Canada H3T 1J4.
Bendayan
Moise
M
Sané
Alain
A
Dominguez
Michel
M
Garofalo
Carole
C
Levy
Emile
E
J Clin Endocrinol Metab. 2005 Nov;90(11):6177-84
16144948
Gastroenterology. 2003 Feb;124(2):470-80
12557152
J Histochem Cytochem. 2006 Jul;54(7):781-94
16517974
Eur J Immunol. 2006 Dec;36(12):3101-4
17125140
J Biol Chem. 1994 Jul 22;269(29):18849-55
8034639
Mol Biol Cell. 1995 May;6(5):597-610
7545032
Gut. 2000 Aug;47(2):178-83
10896907
J Cell Biol. 1989 Dec;109(6 Pt 1):2731-9
2556406
Mol Endocrinol. 2004 Jun;18(6):1354-62
15016839
Peptides. 1999 Dec;20(12):1449-53
10698121
J Cell Sci. 1991 Dec;100 ( Pt 4):753-9
1667660
J Histochem Cytochem. 2005 Jul;53(7):851-60
15995144
Science. 1995 Jul 28;269(5223):540-3
7624776
Am J Physiol Gastrointest Liver Physiol. 2006 Apr;290(4):G805-12
16455789
Diabetologia. 1990 Apr;33(4):197-204
2189769
Curr Opin Clin Nutr Metab Care. 2008 May;11(3):303-8
18403928
J Clin Endocrinol Metab. 1999 Jul;84(7):2336-41
10404799
J Lipid Res. 2008 May;49(5):961-72
18235139
Am J Physiol Gastrointest Liver Physiol. 2006 Feb;290(2):G242-9
16239400
Nature. 1998 Aug 20;394(6695):790-3
9723619
J Biol Chem. 2002 Nov 29;277(48):45898-903
12270921
J Biol Chem. 1998 Oct 2;273(40):26194-201
9748302
J Cell Physiol. 1990 May;143(2):391-5
2332459
J Biol Chem. 1999 Jul 23;274(30):21416-24
10409704
Am J Physiol Endocrinol Metab. 2008 May;294(5):E827-32
18285524
Mol Cell Biol. 1998 Jul;18(7):3862-70
9632770
J Cell Biol. 1994 Dec;127(5):1217-32
7525606
J Clin Invest. 1997 Jan 1;99(1):14-8
9011568
Biochem Biophys Res Commun. 2001 May 18;283(4):982-8
11350082
J Biol Chem. 1988 Dec 5;263(34):18545-52
3192548
Prog Histochem Cytochem. 1995;29(4):1-159
7480783
J Biol Chem. 2004 Jul 2;279(27):28499-508
15123629
Pharm Res. 2007 Sep;24(9):1759-71
17619996
J Clin Invest. 2001 Nov;108(10):1483-94
11714740
Biochem J. 1995 Jun 15;308 ( Pt 3):769-75
8948431
Science. 2001 Feb 16;291(5507):1363-5
11233453
Biochem J. 1994 Oct 15;303 ( Pt 2):647-55
7980428
Can J Physiol Pharmacol. 1997 Mar;75(3):193-8
9164701
Diabetes. 1999 Feb;48(2):279-86
10334302
EMBO J. 2001 Jul 16;20(14):3676-84
11447109
J Cell Sci. 1994 Dec;107 ( Pt 12):3461-8
7706397
Histol Histopathol. 2007 Feb;22(2):199-210
17149693
Am J Physiol Gastrointest Liver Physiol. 2007 Oct;293(4):G773-9
17673543
Nature. 1994 Dec 1;372(6505):425-32
7984236
Proc Natl Acad Sci U S A. 1986 Mar;83(5):1463-6
3081898
J Cell Biol. 1994 Dec;127(5):1199-215
7962085
Microsc Res Tech. 2000 May 15;49(4):374-82
10820521