AC6 regulates the microtubule-depolymerizing kinesin KIF19A to control ciliary length in mammals.

The Journal of Biological Chemistry
Kavisha AroraAnjaparavanda P Naren

Abstract

Motile cilia are hairlike structures that line the respiratory and reproductive tracts and the middle ear and generate fluid flow in these organs via synchronized beating. Cilium growth is a highly regulated process that is assumed to be important for flow generation. Recently, Kif19a, a kinesin residing at the cilia tip, was identified to be essential for ciliary length control through its microtubule depolymerization function. However, there is a lack of information on the nature of proteins and the integrated signaling mechanism regulating growth of motile cilia. Here, we report that adenylate cyclase 6 (AC6), a highly abundant AC isoform in airway epithelial cells, inhibits degradation of Kif19a by inhibiting autophagy, a cellular recycling mechanism for damaged proteins and organelles. Using epithelium-specific knockout mice of AC6, we demonstrated that AC6 knockout airway epithelial cells have longer cilia compared with the WT cells because of decreased Kif19a protein levels in the cilia. We demonstrated in vitro that AC6 inhibits AMP-activated kinase (AMPK), an important modulator of cellular energy-conserving mechanisms, and uncouples its binding with ciliary kinesin Kif19a. In the absence of AC6, activation of AMPK mob...Continue Reading

References

Sep 17, 1998·The Journal of Clinical Investigation·H MatsuiR C Boucher
Oct 22, 2002·American Journal of Physiology. Lung Cellular and Molecular Physiology·Yingjian YouSteven L Brody
Aug 15, 2006·Nature Cell Biology·Vladimir VargaJonathon Howard
Sep 2, 2006·Annual Review of Physiology·Matthias Salathe
Oct 24, 2007·Nature Reviews. Molecular Cell Biology·Manfred FliegaufHeymut Omran
May 8, 2009·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Jonathan L Tobin, Philip L Beales
Oct 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Joseph S StephanPaul K Herman
Dec 18, 2009·PloS One·Philip L LeopoldRonald G Crystal
Jan 26, 2010·Current Biology : CB·Tatiana Y BesschetnovaJagesh V Shah
Jan 25, 2011·Nature Cell Biology·Joungmok KimKun-Liang Guan
Sep 6, 2011·Nature Cell Biology·Maria M Mihaylova, Reuben J Shaw
Oct 18, 2012·Annual Review of Pathology·Lyndsay Murrow, Jayanta Debnath
Nov 22, 2012·Developmental Cell·Shinsuke NiwaNobutaka Hirokawa
Aug 22, 2013·Journal of Visualized Experiments : JoVE·Richard Francis, Cecilia Lo
Oct 4, 2013·Nature·Olatz PampliegaAna Maria Cuervo
Nov 10, 2013·The Journal of Clinical Investigation·Hilaire C LamAugustine M K Choi
Nov 21, 2015·Developmental Cell·David U MickMaxence V Nachury
Nov 2, 2016·Proceedings of the National Academy of Sciences of the United States of America·Bryn S MooreTooraj Mirshahi
Jan 24, 2018·Proceedings of the National Academy of Sciences of the United States of America·Suifang MaoMichael J Welsh

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Citations

Oct 18, 2020·The Journal of Biological Chemistry·Lukas Cajanek
Feb 13, 2021·International Journal of Molecular Sciences·Caroline Amalie Brunbjerg HeyLisbeth Birk Møller
Oct 27, 2021·Physiological Reviews·Katrina F OstromRennolds S Ostrom

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