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KIF13B establishes a CAV1-enriched microdomain at the ciliary transition zone to promote Sonic hedgehog signalling.

Abstract：

:Ciliary membrane composition is controlled by transition zone (TZ) proteins such as RPGRIP1, RPGRIPL and NPHP4, which are vital for balanced coordination of diverse signalling systems like the Sonic hedgehog (Shh) pathway. Activation of this pathway involves Shh-induced ciliary accumulation of Smoothened (SMO), which is disrupted by disease-causing mutations in TZ components. Here we identify kinesin-3 motor protein KIF13B as a novel member of the RPGRIP1N-C2 domain-containing protein family and show that KIF13B regulates TZ membrane composition and ciliary SMO accumulation. KIF13B is upregulated during ciliogenesis and is recruited to the ciliary base by NPHP4, which binds to two distinct sites in the KIF13B tail region, including an RPGRIP1N-C2 domain. KIF13B and NPHP4 are both essential for establishment of a CAV1 membrane microdomain at the TZ, which in turn is required for Shh-induced ciliary SMO accumulation. Thus KIF13B is a novel regulator of ciliary TZ configuration, membrane composition and Shh signalling.

journal_name

Nat Commun

journal_title

Nature communications

authors

Schou KB,Mogensen JB,Morthorst SK,Nielsen BS,Aleliunaite A,Serra-Marques A,Fürstenberg N,Saunier S,Bizet AA,Veland IR,Akhmanova A,Christensen ST,Pedersen LB

doi

10.1038/ncomms14177

subject

Has Abstract

pub_date

2017-01-30 00:00:00

pages

14177

issn

2041-1723

pii

ncomms14177

journal_volume

8

pub_type

杂志文章

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