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

Kenneth Bødtker Schou; Johanne Bay Mogensen; Stine Kjær Morthorst; Brian Skriver Nielsen; Aiste Aleliunaite; Andrea Serra-Marques; Nicoline Fürstenberg; Sophie Saunier; Albane A. Bizet; Iben Rønn Veland; Anna Akhmanova; Søren Tvorup Christensen; Lotte Bang Pedersen

doi:10.1038/ncomms14177

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

Kenneth Bødtker Schou, Johanne Bay Mogensen, Stine Kjær Morthorst, Brian Skriver Nielsen, Aiste Aleliunaite, Andrea Serra-Marques, Nicoline Fürstenberg, Sophie Saunier, Albane A. Bizet, Iben Rønn Veland, Anna Akhmanova, Søren Tvorup Christensen, Lotte Bang Pedersen

Cell Biology and Physiology

30 Citations (Scopus)

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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.

Original language	English
Article number	14177
Journal	Nature Communications
Volume	8
Number of pages	15
ISSN	2041-1723
DOIs	https://doi.org/10.1038/ncomms14177
Publication status	Published - 30 Jan 2017

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Schou, K. B., Mogensen, J. B., Morthorst, S. K., Nielsen, B. S., Aleliunaite, A., Serra-Marques, A., Fürstenberg, N., Saunier, S., Bizet, A. A., Veland, I. R., Akhmanova, A., Christensen, S. T., & Pedersen, L. B. (2017). KIF13B establishes a CAV1-enriched microdomain at the ciliary transition zone to promote Sonic hedgehog signalling. Nature Communications, 8, Article 14177. https://doi.org/10.1038/ncomms14177

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 2017, 'KIF13B establishes a CAV1-enriched microdomain at the ciliary transition zone to promote Sonic hedgehog signalling.', Nature Communications, vol. 8, 14177. https://doi.org/10.1038/ncomms14177

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title = "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.",

author = "Schou, {Kenneth B{\o}dtker} and Mogensen, {Johanne Bay} and Morthorst, {Stine Kj{\ae}r} and Nielsen, {Brian Skriver} and Aiste Aleliunaite and Andrea Serra-Marques and Nicoline F{\"u}rstenberg and Sophie Saunier and Bizet, {Albane A.} and Veland, {Iben R{\o}nn} and Anna Akhmanova and Christensen, {S{\o}ren Tvorup} and Pedersen, {Lotte Bang}",

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AU - Schou, Kenneth Bødtker

AU - Mogensen, Johanne Bay

AU - Morthorst, Stine Kjær

AU - Nielsen, Brian Skriver

AU - Aleliunaite, Aiste

AU - Serra-Marques, Andrea

AU - Fürstenberg, Nicoline

AU - Saunier, Sophie

AU - Bizet, Albane A.

AU - Veland, Iben Rønn

AU - Akhmanova, Anna

AU - Christensen, Søren Tvorup

AU - Pedersen, Lotte Bang

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N2 - 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.

AB - 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.

U2 - 10.1038/ncomms14177

DO - 10.1038/ncomms14177

M3 - Journal article

C2 - 28134340

SN - 2041-1723

VL - 8

JO - Nature Communications

JF - Nature Communications

M1 - 14177

ER -

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

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