The role for HNF-1β-targeted collectrin in maintenance of primary cilia and cell polarity in collecting duct cells

Yanling Zhang, Jun Wada, Akihiro Yasuhara, Izumi Iseda, Jun Eguchi, Kenji Fukui, Qin Yang, Kazuya Yamagata, Thomas Hiesberger, Peter Igarashi, Hong Zhang, Haiyan Wang, Shigeru Akagi, Yashpal S. Kanwar, Hirofumi Makino

Research output: Contribution to journalArticle

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Abstract

Collectrin, a homologue of angiotensin converting enzyme 2 (ACE2), is a type I transmembrane protein, and we originally reported its localization to the cytoplasm and apical membrane of collecting duct cells. Recently, two independent studies of targeted disruption of collectrin in mice resulted in severe and general defects in renal amino acid uptake. Collectrin has been reported to be under the transcriptional regulation by HNF-1α, which is exclusively expressed in proximal tubules and localized at the luminal side of brush border membranes. The deficiency of collectrin was associated with reduction of multiple amino acid transporters on luminal membranes. In the current study, we describe that collectrin is a target of HNF-1β and heavily expressed in the primary cilium of renal collecting duct cells. Collectrin is also localized in the vesicles near the peri-basal body region and binds to γ-actin-myosin II-A, SNARE, and polycystin-2-polaris complexes, and all of these are involved in intracellular and ciliary movement of vesicles and membrane proteins. Treatment of mIMCD3 cells with collectrin siRNA resulted in defective cilium formation, increased cell proliferation and apoptosis, and disappearance of polycystin-2 in the primary cilium. Suppression of collectrin mRNA in metanephric culture resulted in the formation of multiple longitudinal cysts in ureteric bud branches. Taken together, the cystic change and formation of defective cilium with the interference in the collectrin functions would suggest that it is necessary for recycling of the primary cilia-specific membrane proteins, the maintenance of the primary cilia and cell polarity of collecting duct cells. The transcriptional hierarchy between HNF-1β and PKD (polycystic kidney disease) genes expressed in the primary cilia of collecting duct cells has been suggested, and collectrin is one of such HNF-1β regulated genes.

Original languageEnglish (US)
Article numbere414
JournalPLoS One
Volume2
Issue number5
DOIs
StatePublished - May 2 2007

Fingerprint

Cell Polarity
Cilia
cilia
Ducts
Maintenance
Membranes
Membrane Proteins
Genes
cells
Myosin Type II
Amino Acid Transport Systems
SNARE Proteins
membrane proteins
Cell proliferation
Brushes
Small Interfering RNA
Recycling
Actins
kidneys
Basal Bodies

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

The role for HNF-1β-targeted collectrin in maintenance of primary cilia and cell polarity in collecting duct cells. / Zhang, Yanling; Wada, Jun; Yasuhara, Akihiro; Iseda, Izumi; Eguchi, Jun; Fukui, Kenji; Yang, Qin; Yamagata, Kazuya; Hiesberger, Thomas; Igarashi, Peter; Zhang, Hong; Wang, Haiyan; Akagi, Shigeru; Kanwar, Yashpal S.; Makino, Hirofumi.

In: PLoS One, Vol. 2, No. 5, e414, 02.05.2007.

Research output: Contribution to journalArticle

Zhang, Y, Wada, J, Yasuhara, A, Iseda, I, Eguchi, J, Fukui, K, Yang, Q, Yamagata, K, Hiesberger, T, Igarashi, P, Zhang, H, Wang, H, Akagi, S, Kanwar, YS & Makino, H 2007, 'The role for HNF-1β-targeted collectrin in maintenance of primary cilia and cell polarity in collecting duct cells', PLoS One, vol. 2, no. 5, e414. https://doi.org/10.1371/journal.pone.0000414
Zhang, Yanling ; Wada, Jun ; Yasuhara, Akihiro ; Iseda, Izumi ; Eguchi, Jun ; Fukui, Kenji ; Yang, Qin ; Yamagata, Kazuya ; Hiesberger, Thomas ; Igarashi, Peter ; Zhang, Hong ; Wang, Haiyan ; Akagi, Shigeru ; Kanwar, Yashpal S. ; Makino, Hirofumi. / The role for HNF-1β-targeted collectrin in maintenance of primary cilia and cell polarity in collecting duct cells. In: PLoS One. 2007 ; Vol. 2, No. 5.
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abstract = "Collectrin, a homologue of angiotensin converting enzyme 2 (ACE2), is a type I transmembrane protein, and we originally reported its localization to the cytoplasm and apical membrane of collecting duct cells. Recently, two independent studies of targeted disruption of collectrin in mice resulted in severe and general defects in renal amino acid uptake. Collectrin has been reported to be under the transcriptional regulation by HNF-1α, which is exclusively expressed in proximal tubules and localized at the luminal side of brush border membranes. The deficiency of collectrin was associated with reduction of multiple amino acid transporters on luminal membranes. In the current study, we describe that collectrin is a target of HNF-1β and heavily expressed in the primary cilium of renal collecting duct cells. Collectrin is also localized in the vesicles near the peri-basal body region and binds to γ-actin-myosin II-A, SNARE, and polycystin-2-polaris complexes, and all of these are involved in intracellular and ciliary movement of vesicles and membrane proteins. Treatment of mIMCD3 cells with collectrin siRNA resulted in defective cilium formation, increased cell proliferation and apoptosis, and disappearance of polycystin-2 in the primary cilium. Suppression of collectrin mRNA in metanephric culture resulted in the formation of multiple longitudinal cysts in ureteric bud branches. Taken together, the cystic change and formation of defective cilium with the interference in the collectrin functions would suggest that it is necessary for recycling of the primary cilia-specific membrane proteins, the maintenance of the primary cilia and cell polarity of collecting duct cells. The transcriptional hierarchy between HNF-1β and PKD (polycystic kidney disease) genes expressed in the primary cilia of collecting duct cells has been suggested, and collectrin is one of such HNF-1β regulated genes.",
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AU - Zhang, Yanling

AU - Wada, Jun

AU - Yasuhara, Akihiro

AU - Iseda, Izumi

AU - Eguchi, Jun

AU - Fukui, Kenji

AU - Yang, Qin

AU - Yamagata, Kazuya

AU - Hiesberger, Thomas

AU - Igarashi, Peter

AU - Zhang, Hong

AU - Wang, Haiyan

AU - Akagi, Shigeru

AU - Kanwar, Yashpal S.

AU - Makino, Hirofumi

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