The Spinocerebellar Ataxia-Associated Gene Tau Tubulin Kinase 2 Controls the Initiation of Ciliogenesis

Authors

Sarah C. Goetz, Karel F. Liem, Kathryn V. Andersonsend emailSee Affiliations
  • Hint: Rollover Authors and Affiliations
Developmental Biology Program, Sloan-Kettering Institute, 1275 York Avenue, New York, NY 10065, USA Corresponding author Present address: Vertebrate Developmental Biology Program, Department of Pediatrics, Yale School of Medicine, New Haven, CT 06520, USA
  • Highlights
Tau tubulin kinase 2
(
Ttbk2
) is essential for mouse Shh signaling and ciliogenesis ► TTBK2 recruits IFT proteins and removes CP110 from the mother centriole ► TTBK2 recruitment to the basal body correlates with the removal of CP110 ► Human
TTBK2
mutations that cause SCA11 inhibit cilia formation in wild-type cells

Summary

The primary cilium has critical roles in human development and disease, but the mechanisms that regulate ciliogenesis are not understood. Here, we show that Tau tubulin kinase 2 (TTBK2) is a dedicated regulator of the initiation of ciliogenesis in vivo. We identified a null allele of mouse Ttbk2 based on loss of Sonic hedgehog activity, a signaling pathway that requires the primary cilium. Despite a normal basal body template, Ttbk2 mutants lack cilia. TTBK2 acts at the distal end of the basal body, where it promotes the removal of CP110, which caps the mother centriole, and promotes recruitment of IFT proteins, which build the ciliary axoneme. Dominant truncating mutations in human TTBK2 cause spinocerebellar ataxia type 11 (SCA11); these mutant proteins do not promote ciliogenesis and inhibit ciliogenesis in wild-type cells. We propose that cell-cycle regulators target TTBK2 to the basal body, where it modifies specific targets to initiate ciliogenesis.

from http://www.cell.com/abstract/S0092-8674(12)01224-X

Thank you, Alan. It seems as if the cell cycle regulator - based therapies are upcoming, also in Ataxia (till now, to my knowledge there has been research mainly for cancer.)

Kind regards,

Margarete

Hi Alan,

i wonder in what you were interested in by posting this. Quite difficult to understand.. I have read a lot two days ago and found out that i first have to learn what the special terms mean, and how this all functions with the cell cycle...

(and: could you please, help me how to start a new discussion? thanx in advance )

Akita

I tend to post most things relating to Ataxia (or indeed rarediseases) (from General information to very complicated medical, based info.)

"sharing of Information" for the benefit / satisfaction of all people

to start a new disscusion, click on FORUM and then click ADD

type in the box a title for you post

then , in the large box, type in your message

then click the ADD DISSCUSION button at the bottom of the page.

Alan

Dear Alan,

thanks for the info regarding the forum-discussions.


Hopefully we will be able to celebrate soon a success in the Ataxia Research which will stop the disease for most of the patients.

Kind regards,

Akita