Compensatory endocytosis in bladder umbrella cells occurs through an integrin-regulated and RhoA- and dynamin-dependent pathway.
Compensatory endocytosis (CE) ensures recycling of membrane components and maintenance of plasma membrane size; however, the mechanisms, regulation, and physiological functions of clathrin-independent modes of CE are poorly understood. CE was studied in umbrella cells, which undergo regulated exocytosis of subapical discoidal/fusiform vesicles (DFV) during bladder filling, and may then replenish the pool of DFV by internalizing apical membrane during voiding. We found that voiding-stimulated CE, which depended on beta(1) integrin-associated signalling pathways, occurred by a dynamin-, actin-, and RhoA-regulated mechanism and was independent of caveolins, clathrin, and flotillin. Internalized apical membrane and fluid were initially found in ZO-1-positive vesicles, which were distinct from DFV, classical early endosomes, or the Golgi, and subsequently in lysosomes. We conclude that clathrin-independent CE in umbrella cells functions to recover membrane during voiding, is integrin regulated, occurs by a RhoA- and dynamin-dependent pathway, and terminates in degradation and not recapture of membrane in DFV.
Khandelwal
Puneet
P
Department of Medicine, Laboratory of Epithelial Cell Biology and Renal-Electrolyte Division, University of Pittsburgh, Pittsburgh, PA, USA.
Ruiz
Wily G
WG
Apodaca
Gerard
G
D000199:Actins / Q000378:metabolism; D000818:Animals; D022461:Caveolins / Q000378:metabolism; D002966:Clathrin / Q000378:metabolism; D034281:Dynamins / Q000378:metabolism*; D004705:Endocytosis; D019012:Integrin beta1 / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D011817:Rabbits; D022161:Transport Vesicles / Q000502:physiology; D001743:Urinary Bladder / Q000502:physiology*; D019459:Urothelium / Q000502:physiology*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D000199:Actins; D022461:Caveolins; D002966:Clathrin; D019012:Integrin beta1; D008565:Membrane Proteins; C106354:flotillins; D020742:rhoA GTP-Binding Protein; D034281:Dynamins
Acta Physiol (Oxf). 2008 Feb;192(2):195-201
18021324
Cell. 1999 Oct 15;99(2):179-88
10535736
Trends Neurosci. 2007 Sep;30(9):447-55
17765328
Biochem Biophys Res Commun. 2007 Jun 15;357(4):834-9
17451644
Nat Rev Mol Cell Biol. 2003 Feb;4(2):127-39
12563290
J Neurosci. 2007 Oct 31;27(44):11793-802
17978015
Proc Natl Acad Sci U S A. 2002 May 14;99(10):7124-9
11997474
Exp Cell Res. 2003 Nov 1;290(2):322-31
14567990
Dev Cell. 2007 Jul;13(1):43-56
17609109
Nature. 1982 Jun 24;297(5868):685-8
6283364
Nat Cell Biol. 2003 Aug;5(8):727-32
12872130
Nat Rev Mol Cell Biol. 2007 Aug;8(8):603-12
17609668
Nature. 2003 Dec 4;426(6966):559-63
14634669
Nat Rev Mol Cell Biol. 2005 Jan;6(1):56-68
15688067
Dev Cell. 2006 Jun;10(6):839-50
16740485
Am J Physiol Cell Physiol. 2007 Jun;292(6):C2057-69
17267546
J Exp Zool. 2000 Jun 1;286(7):767-75
10797329
Cell Adhes Commun. 1995 Aug;3(3):231-42
8846024
Mol Biol Cell. 2009 Jan;20(1):282-95
18987341
Methods. 2003 Jul;30(3):207-17
12798135
Methods Cell Biol. 1989;31:553-69
2674632
EMBO J. 2001 Sep 3;20(17):4639-47
11532928
Mol Biol Cell. 2007 Oct;18(10):4096-105
17699600
Biochim Biophys Acta. 2001 Jul 25;1540(1):1-21
11476890
Am J Physiol Heart Circ Physiol. 2005 Oct;289(4):H1488-96
15923313
Proc Natl Acad Sci U S A. 2008 Oct 14;105(41):15773-8
18843107
J Biol Chem. 1999 May 21;274(21):15020-9
10329705
Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):6358-63
11959911
J Cell Sci. 2001 Dec;114(Pt 24):4613-20
11792825
Curr Biol. 2007 Jul 3;17(13):1151-6
17600709
J Physiol. 2007 Dec 15;585(Pt 3):687-91
17584836
Am J Clin Pathol. 2003 Jul;120(1):93-100
12866378
J Cell Biol. 1994 Nov;127(4):915-34
7962076
J Cell Biol. 2000 Feb 21;148(4):755-67
10684256
Mol Biol Cell. 2004 Aug;15(8):3542-52
15146059
J Cell Biol. 1991 Dec;115(6):1573-84
1757463
J Neurosci. 2008 Jun 25;28(26):6627-32
18579735
Science. 2004 Feb 6;303(5659):839-42
14764880
Eur J Histochem. 2006 Jul-Sep;50(3):183-90
16920641
J Biol Chem. 2004 Sep 3;279(36):37544-50
15184362
Am J Respir Cell Mol Biol. 2004 Mar;30(3):288-95
12933357
Nat Biotechnol. 1998 Jan;16(1):75-9
9447598
Cell Tissue Res. 2009 Jul;337(1):91-102
19479281
Methods Mol Biol. 2008;440:15-33
18369934
Dev Cell. 2002 Apr;2(4):411-23
11970892
Mol Biol Cell. 2006 Apr;17(4):1495-502
16436510
Pediatr Nephrol. 2004 Jul;19(7):714-21
15146321
J Cell Sci. 1996 Feb;109 ( Pt 2):457-65
8838669
Trends Cell Biol. 2006 Oct;16(10):487-92
16949286
J Cell Biol. 1988 Apr;106(4):1141-9
2452168
Traffic. 2004 Jul;5(7):463-9
15180823
J Cell Sci. 2009 Jun 1;122(Pt 11):1852-62
19435801
Histochem Cell Biol. 2008 Mar;129(3):267-76
18193449
Traffic. 2010 Mar;11(3):348-60
20051050
J Cell Biol. 2008 Jan 14;180(1):187-203
18195107
Mol Cell. 2001 Mar;7(3):661-71
11463390
FEBS Lett. 2004 Jul 30;571(1-3):103-6
15280025
Differentiation. 2009 Jan;77(1):48-59
19281764
Cell. 2009 Jun 26;137(7):1308-19
19563761
Nat Cell Biol. 2004 Nov;6(11):1102-8
15475946
Cell. 2009 Sep 4;138(5):947-60
19737521
Nat Neurosci. 2008 Jan;11(1):45-53
18066059
Philos Trans R Soc Lond B Biol Sci. 1974 Jul 25;268(891):23-38
4155088
J Biol Chem. 1990 Nov 5;265(31):19170-9
2229070
Curr Biol. 2008 Nov 25;18(22):1802-8
19036340
EMBO Rep. 2008 Apr;9(4):356-62
18344974
Nat Rev Mol Cell Biol. 2009 Sep;10(9):583-96
19696796
J Cell Sci. 2009 Jun 1;122(Pt 11):1713-21
19461071
Exp Cell Res. 2004 Nov 15;301(1):23-30
15501441
Mol Biol Cell. 2007 Apr;18(4):1312-23
17287395
Anat Rec. 1991 Jan;229(1):9-15
1996788
Am J Physiol Renal Physiol. 2009 Dec;297(6):F1477-501
19587142
Neuron. 2005 Jun 16;46(6):869-78
15953416
Mol Biol Cell. 2002 Mar;13(3):830-46
11907265
Eur J Cell Biol. 2003 Jul;82(7):343-50
12924629
J Neurosci. 2003 Feb 15;23(4):1329-39
12598621
J Cell Mol Med. 2008 Jan-Feb;12(1):126-44
18039352
J Physiol. 1998 Feb 1;506 ( Pt 3):591-608
9503324
Traffic. 2007 Jun;8(6):702-17
17461795
Nat Cell Biol. 2005 Sep;7(9):901-8
16113676
Kidney Int. 2009 Jun;75(11):1153-1165
19340092
Proc Natl Acad Sci U S A. 2000 Feb 1;97(3):1091-5
10655489