Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0202400
Title: Association of crumbs homolog-2 with mTORC1 in developing podocyte
Authors: Hamano S.
Nishibori Y.
Hada I.
Mikami N.
Ito-Nitta N.
Fukuhara D.
Kudo A.
Xiao Z.
Nukui M.
Patrakka J.
Tryggvason K. 
Yan K.
Keywords: mammalian target of rapamycin complex 1
tyrosine
carrier protein
CRB2 protein, human
Crb2 protein, mouse
mammalian target of rapamycin complex 1
membrane protein
adult
animal cell
animal experiment
Article
cell maturation
cell membrane
confocal microscopy
controlled study
CRB2 gene
energy
enzyme activation
gene
gene function
genetic association
HEK293 cell line
male
MDCK cell line
mouse
newborn
nonhuman
podocyte
protein assembly
protein glycosylation
protein localization
protein phosphorylation
sensitivity analysis
signal transduction
stem cell
animal
cytology
dog
genetics
glycosylation
human
metabolism
phosphorylation
podocyte
Animals
Carrier Proteins
Cell Membrane
Dogs
Glycosylation
HEK293 Cells
Humans
Madin Darby Canine Kidney Cells
Male
Mechanistic Target of Rapamycin Complex 1
Membrane Proteins
Mice
Phosphorylation
Podocytes
Stem Cells
Issue Date: 2018
Citation: Hamano S., Nishibori Y., Hada I., Mikami N., Ito-Nitta N., Fukuhara D., Kudo A., Xiao Z., Nukui M., Patrakka J., Tryggvason K., Yan K. (2018). Association of crumbs homolog-2 with mTORC1 in developing podocyte. PLoS ONE 13 (8) : e0202400. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0202400
Rights: Attribution 4.0 International
Abstract: The evidence that gene mutations in the polarity determinant Crumbs homologs-2 (CRB2) cause congenital nephrotic syndrome suggests the functional importance of this gene product in podocyte development. Because another isoform, CRB3, was reported to repress the mechanistic/mammalian target of the rapamycin complex 1 (mTORC1) pathway, we examined the role of CRB2 function in developing podocytes in relation to mTORC1. In HEK-293 and MDCK cells constitutively expressing CRB2, we found that the protein localized to the apicolateral side of the cell plasma membrane and that this plasma membrane assembly required N-glycosylation. Confocal microscopy of the neonate mouse kidney revealed that both the tyrosine-phosphorylated form and non-phosphorylated form of CRB2 commence at the S-shaped body stage at the apicolateral side of podocyte precursor cells and move to foot processes in a capillary tuft pattern. The pattern of phosphorylated mTOR in developing podocytes was similar to that of CRB2 tyrosine phosphorylation. Additionally, the lack of a tyrosine phosphorylation site on CRB2 led to the reduced sensitivity of mTORC1 activation in response to energy starvation. CRB2 may play an important role in the mechanistic pathway of developing podocytes through tyrosine phosphorylation by associating with mTORC1 activation. © 2018 Hamano et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/161217
ISSN: 19326203
DOI: 10.1371/journal.pone.0202400
Rights: Attribution 4.0 International
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