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SUMMARY:Regulatory mechanisms of ciliary protein transport through Ccrk-Ma
 k/Ick kinase signaling in retinal photoreceptor cells - Dr Yamato Maeda\, 
 Research fellow\, Institute for Protein Research\, Osaka University\, Japa
 n
DTSTART:20241216T120000Z
DTEND:20241216T130000Z
UID:TALK225475@talks.cam.ac.uk
CONTACT:Keita Tamura
DESCRIPTION:Primary cilia are hair-like microtubule-based structures whose
  dysfunction leads to human diseases termed ciliopathies. The formation\, 
 function\, and maintenance of primary cilia rely on ciliary protein transp
 ort systems including lipidated protein intraflagellar targeting (LIFT) an
 d intraflagellar transport (IFT). We previously reported that CUL3-KLHL18 
 ubiquitin ligase regulates light-dark adaptation of retinal photoreceptor 
 cells through modulating LIFT (1). However\, the regulatory mechanisms und
 erlying ciliary protein transport remain unclear. Here\, we identified tha
 t the ciliopathy kinase Mak is a ciliary tip-localized IFT regulator that 
 functions with the ciliopathy kinase Ick\, as an IFT regulator at ciliary 
 tips. Disruption of both Mak and Ick caused loss of photoreceptor ciliary 
 axonemes and severe progressive retinal degeneration. Gene delivery of Ick
  and pharmacological activation of Ick with an FGF receptors inhibitor ame
 liorated ciliopathy-related retinal degeneration in Mak−/− mice. Addit
 ionally\, we found that Ccrk kinase is an upstream activator of Mak and Ic
 k in retinal photoreceptor cells. This study suggests that the Ccrk-Mak/Ic
 k axis is an IFT turnaround regulator essential for retinal photoreceptor 
 maintenance and presents activation of Ick as a potential therapeutic appr
 oach for retinitis pigmentosa caused by MAK mutations (2).
LOCATION:Bryan Matthews Seminar Room\, Physiological Laboratory building\,
  Department of Physiology\, Development and Neuroscience
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