Abstract

Membrane morphology is an important structural determinant as it reflects cellular functions. The pentaspan membrane protein Prominin-1 (Prom1/CD133) is known to be localised to protrusions and plays a pivotal role in migration and the determination of cellular morphology; however, the underlying mechanism of its action have been elusive. Here, we performed molecular characterisation of Prom1, focussing primarily on its effects on cell morphology. Overexpression of Prom1 in RPE-1 cells triggers multiple, long, cholesterol-enriched fibres, independently of actin and microtubule polymerisation. A five amino acid stretch located at the carboxyl cytosolic region is essential for fibre formation. The small GTPase Rho and its downstream Rho-associated coiled-coil-containing protein kinase (ROCK) are also essential for this process, and active Rho colocalises with Prom1 at the site of initialisation of fibre formation. In mouse embryonic fibroblast (MEF) cells we show that Prom1 is required for chloride ion efflux induced by calcium ion uptake, and demonstrate that fibre formation is closely associated with chloride efflux activity. Collectively, these findings suggest that Prom1 affects cell morphology and contributes to chloride conductance.

Details

Title
Prominin-1 Modulates Rho/ROCK-Mediated Membrane Morphology and Calcium-Dependent Intracellular Chloride Flux
Author
Hori, Akiko 1 ; Nishide, Kenji 2 ; Yasukuni, Yuki 1 ; Haga, Kei 1 ; Kakuta, Wataru 1 ; Ishikawa, Yasuyuki 3 ; Hayes, Matthew J 4 ; Ohnuma, Shin-ichi 4 ; Kiyonari, Hiroshi 5 ; Kimura, Kazuhiro 6 ; Kondo, Toru 7 ; Sasai, Noriaki 1 

 Developmental Biomedical Science, Division of Biological Sciences, Nara Institute of Science and Technology, 8916-5, Takayama-cho, Ikoma, Japan 
 Laboratory for Cell Lineage Modulation, Center for Developmental Biology, Chuo-ku, Kobe, Japan 
 Department of Systems Life Engineering, Maebashi Institute of Technology, Maebashi, Gunma, Japan 
 Faculty of Brain Sciences, UCL Institute of Ophthalmology, University College London, London, United Kingdom 
 Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Biosystems Dynamics Research, Chuo-ku, Kobe, Japan 
 Department of Ophthalmology, Yamaguchi University School of Medicine, Ube, Japan 
 Laboratory for Cell Lineage Modulation, Center for Developmental Biology, Chuo-ku, Kobe, Japan; Division of Stem Cell Biology, Institute for Genetic Medicine, Hokkaido University, Kita-Ku, Sapporo, Japan 
Pages
1-13
Publication year
2019
Publication date
Nov 2019
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2311941340
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.