Cargando…

MAL facilitates the incorporation of exocytic uroplakin-delivering vesicles into the apical membrane of urothelial umbrella cells

The apical surface of mammalian bladder urothelium is covered by large (500–1000 nm) two-dimensional (2D) crystals of hexagonally packed 16-nm uroplakin particles (urothelial plaques), which play a role in permeability barrier function and uropathogenic bacterial binding. How the uroplakin proteins...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhou, Ge, Liang, Feng-Xia, Romih, Rok, Wang, Zefang, Liao, Yi, Ghiso, Jorge, Luque-Garcia, Jose L., Neubert, Thomas A., Kreibich, Gert, Alonso, Miguel A., Schaeren-Wiemers, Nicole, Sun, Tung-Tien
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3315800/
https://www.ncbi.nlm.nih.gov/pubmed/22323295
http://dx.doi.org/10.1091/mbc.E11-09-0823
_version_ 1782228290163965952
author Zhou, Ge
Liang, Feng-Xia
Romih, Rok
Wang, Zefang
Liao, Yi
Ghiso, Jorge
Luque-Garcia, Jose L.
Neubert, Thomas A.
Kreibich, Gert
Alonso, Miguel A.
Schaeren-Wiemers, Nicole
Sun, Tung-Tien
author_facet Zhou, Ge
Liang, Feng-Xia
Romih, Rok
Wang, Zefang
Liao, Yi
Ghiso, Jorge
Luque-Garcia, Jose L.
Neubert, Thomas A.
Kreibich, Gert
Alonso, Miguel A.
Schaeren-Wiemers, Nicole
Sun, Tung-Tien
author_sort Zhou, Ge
collection PubMed
description The apical surface of mammalian bladder urothelium is covered by large (500–1000 nm) two-dimensional (2D) crystals of hexagonally packed 16-nm uroplakin particles (urothelial plaques), which play a role in permeability barrier function and uropathogenic bacterial binding. How the uroplakin proteins are delivered to the luminal surface is unknown. We show here that myelin-and-lymphocyte protein (MAL), a 17-kDa tetraspan protein suggested to be important for the apical sorting of membrane proteins, is coexpressed with uroplakins in differentiated urothelial cell layers. MAL depletion in Madin–Darby canine kidney cells did not affect, however, the apical sorting of uroplakins, but it decreased the rate by which uroplakins were inserted into the apical surface. Moreover, MAL knockout in vivo led to the accumulation of fusiform vesicles in mouse urothelial superficial umbrella cells, whereas MAL transgenic overexpression in vivo led to enhanced exocytosis and compensatory endocytosis, resulting in the accumulation of the uroplakin-degrading multivesicular bodies. Finally, although MAL and uroplakins cofloat in detergent-resistant raft fractions, they are associated with distinct plaque and hinge membrane subdomains, respectively. These data suggest a model in which 1) MAL does not play a role in the apical sorting of uroplakins; 2) the propensity of uroplakins to polymerize forming 16-nm particles and later large 2D crystals that behave as detergent-resistant (giant) rafts may drive their apical targeting; 3) the exclusion of MAL from the expanding 2D crystals of uroplakins explains the selective association of MAL with the hinge areas in the uroplakin-delivering fusiform vesicles, as well as at the apical surface; and 4) the hinge-associated MAL may play a role in facilitating the incorporation of the exocytic uroplakin vesicles into the corresponding hinge areas of the urothelial apical surface.
format Online
Article
Text
id pubmed-3315800
institution National Center for Biotechnology Information
language English
publishDate 2012
publisher The American Society for Cell Biology
record_format MEDLINE/PubMed
spelling pubmed-33158002012-06-16 MAL facilitates the incorporation of exocytic uroplakin-delivering vesicles into the apical membrane of urothelial umbrella cells Zhou, Ge Liang, Feng-Xia Romih, Rok Wang, Zefang Liao, Yi Ghiso, Jorge Luque-Garcia, Jose L. Neubert, Thomas A. Kreibich, Gert Alonso, Miguel A. Schaeren-Wiemers, Nicole Sun, Tung-Tien Mol Biol Cell Articles The apical surface of mammalian bladder urothelium is covered by large (500–1000 nm) two-dimensional (2D) crystals of hexagonally packed 16-nm uroplakin particles (urothelial plaques), which play a role in permeability barrier function and uropathogenic bacterial binding. How the uroplakin proteins are delivered to the luminal surface is unknown. We show here that myelin-and-lymphocyte protein (MAL), a 17-kDa tetraspan protein suggested to be important for the apical sorting of membrane proteins, is coexpressed with uroplakins in differentiated urothelial cell layers. MAL depletion in Madin–Darby canine kidney cells did not affect, however, the apical sorting of uroplakins, but it decreased the rate by which uroplakins were inserted into the apical surface. Moreover, MAL knockout in vivo led to the accumulation of fusiform vesicles in mouse urothelial superficial umbrella cells, whereas MAL transgenic overexpression in vivo led to enhanced exocytosis and compensatory endocytosis, resulting in the accumulation of the uroplakin-degrading multivesicular bodies. Finally, although MAL and uroplakins cofloat in detergent-resistant raft fractions, they are associated with distinct plaque and hinge membrane subdomains, respectively. These data suggest a model in which 1) MAL does not play a role in the apical sorting of uroplakins; 2) the propensity of uroplakins to polymerize forming 16-nm particles and later large 2D crystals that behave as detergent-resistant (giant) rafts may drive their apical targeting; 3) the exclusion of MAL from the expanding 2D crystals of uroplakins explains the selective association of MAL with the hinge areas in the uroplakin-delivering fusiform vesicles, as well as at the apical surface; and 4) the hinge-associated MAL may play a role in facilitating the incorporation of the exocytic uroplakin vesicles into the corresponding hinge areas of the urothelial apical surface. The American Society for Cell Biology 2012-04-01 /pmc/articles/PMC3315800/ /pubmed/22323295 http://dx.doi.org/10.1091/mbc.E11-09-0823 Text en © 2012 Zhou et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Zhou, Ge
Liang, Feng-Xia
Romih, Rok
Wang, Zefang
Liao, Yi
Ghiso, Jorge
Luque-Garcia, Jose L.
Neubert, Thomas A.
Kreibich, Gert
Alonso, Miguel A.
Schaeren-Wiemers, Nicole
Sun, Tung-Tien
MAL facilitates the incorporation of exocytic uroplakin-delivering vesicles into the apical membrane of urothelial umbrella cells
title MAL facilitates the incorporation of exocytic uroplakin-delivering vesicles into the apical membrane of urothelial umbrella cells
title_full MAL facilitates the incorporation of exocytic uroplakin-delivering vesicles into the apical membrane of urothelial umbrella cells
title_fullStr MAL facilitates the incorporation of exocytic uroplakin-delivering vesicles into the apical membrane of urothelial umbrella cells
title_full_unstemmed MAL facilitates the incorporation of exocytic uroplakin-delivering vesicles into the apical membrane of urothelial umbrella cells
title_short MAL facilitates the incorporation of exocytic uroplakin-delivering vesicles into the apical membrane of urothelial umbrella cells
title_sort mal facilitates the incorporation of exocytic uroplakin-delivering vesicles into the apical membrane of urothelial umbrella cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3315800/
https://www.ncbi.nlm.nih.gov/pubmed/22323295
http://dx.doi.org/10.1091/mbc.E11-09-0823
work_keys_str_mv AT zhouge malfacilitatestheincorporationofexocyticuroplakindeliveringvesiclesintotheapicalmembraneofurothelialumbrellacells
AT liangfengxia malfacilitatestheincorporationofexocyticuroplakindeliveringvesiclesintotheapicalmembraneofurothelialumbrellacells
AT romihrok malfacilitatestheincorporationofexocyticuroplakindeliveringvesiclesintotheapicalmembraneofurothelialumbrellacells
AT wangzefang malfacilitatestheincorporationofexocyticuroplakindeliveringvesiclesintotheapicalmembraneofurothelialumbrellacells
AT liaoyi malfacilitatestheincorporationofexocyticuroplakindeliveringvesiclesintotheapicalmembraneofurothelialumbrellacells
AT ghisojorge malfacilitatestheincorporationofexocyticuroplakindeliveringvesiclesintotheapicalmembraneofurothelialumbrellacells
AT luquegarciajosel malfacilitatestheincorporationofexocyticuroplakindeliveringvesiclesintotheapicalmembraneofurothelialumbrellacells
AT neubertthomasa malfacilitatestheincorporationofexocyticuroplakindeliveringvesiclesintotheapicalmembraneofurothelialumbrellacells
AT kreibichgert malfacilitatestheincorporationofexocyticuroplakindeliveringvesiclesintotheapicalmembraneofurothelialumbrellacells
AT alonsomiguela malfacilitatestheincorporationofexocyticuroplakindeliveringvesiclesintotheapicalmembraneofurothelialumbrellacells
AT schaerenwiemersnicole malfacilitatestheincorporationofexocyticuroplakindeliveringvesiclesintotheapicalmembraneofurothelialumbrellacells
AT suntungtien malfacilitatestheincorporationofexocyticuroplakindeliveringvesiclesintotheapicalmembraneofurothelialumbrellacells