Cholangiocyte Myosin IIB Is Required for Localized Aggregation of Sodium Glucose Cotransporter 1 to Sites of Cryptosporidium parvum Cellular Invasion and Facilitates Parasite Internalization

Internalization of the obligate intracellular apicomplexan parasite, Cryptosporidium parvum, results in the formation of a unique intramembranous yet extracytoplasmic niche on the apical surfaces of host epithelial cells, a process that depends on host cell membrane extension. We previously demonstr...

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Idioma:en
Publicado em: American Society for Microbiology (ASM) 2010
Assuntos:
Cellular Microbiology: Pathogen-Host Cell Molecular Interactions
Acesso em linha:https://ncbi.nlm.nih.gov/pmc/articles/PMC2897363/
https://ncbi.nlm.nih.gov/pubmed/20457792
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1128/IAI.00077-10
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id pubmed-2897363
record_format dspace
institution US National Library of Medicine
collection PubMed Central
language en
format Article
topic Cellular Microbiology: Pathogen-Host Cell Molecular Interactions
spellingShingle Cellular Microbiology: Pathogen-Host Cell Molecular Interactions
Cholangiocyte Myosin IIB Is Required for Localized Aggregation of Sodium Glucose Cotransporter 1 to Sites of Cryptosporidium parvum Cellular Invasion and Facilitates Parasite Internalization
topic_facet Cellular Microbiology: Pathogen-Host Cell Molecular Interactions
description Internalization of the obligate intracellular apicomplexan parasite, Cryptosporidium parvum, results in the formation of a unique intramembranous yet extracytoplasmic niche on the apical surfaces of host epithelial cells, a process that depends on host cell membrane extension. We previously demonstrated that efficient C. parvum invasion of biliary epithelial cells (cholangiocytes) requires host cell actin polymerization and localized membrane translocation/insertion of Na(+)/glucose cotransporter 1 (SGLT1) and of aquaporin 1 (Aqp1), a water channel, at the attachment site. The resultant localized water influx facilitates parasite cellular invasion by promoting host-cell membrane protrusion. However, the molecular mechanisms by which C. parvum induces membrane translocation/insertion of SGLT1/Aqp1 are obscure. We report here that cultured human cholangiocytes express several nonmuscle myosins, including myosins IIA and IIB. Moreover, C. parvum infection of cultured cholangiocytes results in the localized selective aggregation of myosin IIB but not myosin IIA at the region of parasite attachment, as assessed by dual-label immunofluorescence confocal microscopy. Concordantly, treatment of cells with the myosin light chain kinase inhibitor ML-7 or the myosin II-specific inhibitor blebbistatin or selective RNA-mediated repression of myosin IIB significantly inhibits (P < 0.05) C. parvum cellular invasion (by 60 to 80%). Furthermore ML-7 and blebbistatin significantly decrease (P < 0.02) C. parvum-induced accumulation of SGLT1 at infection sites (by approximately 80%). Thus, localized actomyosin-dependent membrane translocation of transporters/channels initiated by C. parvum is essential for membrane extension and parasite internalization, a phenomenon that may also be relevant to the mechanisms of cell membrane protrusion in general.
author_sort O'Hara, Steven P.
title Cholangiocyte Myosin IIB Is Required for Localized Aggregation of Sodium Glucose Cotransporter 1 to Sites of Cryptosporidium parvum Cellular Invasion and Facilitates Parasite Internalization
title_short Cholangiocyte Myosin IIB Is Required for Localized Aggregation of Sodium Glucose Cotransporter 1 to Sites of Cryptosporidium parvum Cellular Invasion and Facilitates Parasite Internalization
title_full Cholangiocyte Myosin IIB Is Required for Localized Aggregation of Sodium Glucose Cotransporter 1 to Sites of Cryptosporidium parvum Cellular Invasion and Facilitates Parasite Internalization
title_fullStr Cholangiocyte Myosin IIB Is Required for Localized Aggregation of Sodium Glucose Cotransporter 1 to Sites of Cryptosporidium parvum Cellular Invasion and Facilitates Parasite Internalization
title_full_unstemmed Cholangiocyte Myosin IIB Is Required for Localized Aggregation of Sodium Glucose Cotransporter 1 to Sites of Cryptosporidium parvum Cellular Invasion and Facilitates Parasite Internalization
title_sort cholangiocyte myosin iib is required for localized aggregation of sodium glucose cotransporter 1 to sites of cryptosporidium parvum cellular invasion and facilitates parasite internalization
publisher American Society for Microbiology (ASM)
publisher_facet American Society for Microbiology (ASM)
publishDate 2010
url https://ncbi.nlm.nih.gov/pmc/articles/PMC2897363/
https://ncbi.nlm.nih.gov/pubmed/20457792
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1128/IAI.00077-10
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