A novel protein LZTFL1 regulates ciliary trafficking of the BBSome and Smoothened

Seongjin Seo; Qihong Zhang; Kevin Bugge; David K Breslow; Charles C Searby; Maxence V Nachury; Val C Sheffield

doi:10.1371/journal.pgen.1002358

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A novel protein LZTFL1 regulates ciliary trafficking of the BBSome and Smoothened

Journal article

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A novel protein LZTFL1 regulates ciliary trafficking of the BBSome and Smoothened

Seongjin Seo, Qihong Zhang, Kevin Bugge, David K Breslow, Charles C Searby, Maxence V Nachury and Val C Sheffield

PLoS genetics, Vol.7(11), e1002358

11/2011

DOI: 10.1371/journal.pgen.1002358

PMCID: PMC3207910

PMID: 22072986

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Abstract

Many signaling proteins including G protein-coupled receptors localize to primary cilia, regulating cellular processes including differentiation, proliferation, organogenesis, and tumorigenesis. Bardet-Biedl Syndrome (BBS) proteins are involved in maintaining ciliary function by mediating protein trafficking to the cilia. However, the mechanisms governing ciliary trafficking by BBS proteins are not well understood. Here, we show that a novel protein, Leucine-zipper transcription factor-like 1 (LZTFL1), interacts with a BBS protein complex known as the BBSome and regulates ciliary trafficking of this complex. We also show that all BBSome subunits and BBS3 (also known as ARL6) are required for BBSome ciliary entry and that reduction of LZTFL1 restores BBSome trafficking to cilia in BBS3 and BBS5 depleted cells. Finally, we found that BBS proteins and LZTFL1 regulate ciliary trafficking of hedgehog signal transducer, Smoothened. Our findings suggest that LZTFL1 is an important regulator of BBSome ciliary trafficking and hedgehog signaling.

Signal Transduction

RNA, Small Interfering - genetics

Bardet-Biedl Syndrome - metabolism

Microtubule-Associated Proteins - genetics

Receptors, G-Protein-Coupled - metabolism

Microtubule-Associated Proteins - metabolism

Humans

Mice, Inbred C57BL

Hedgehog Proteins - metabolism

Mice, Transgenic

Transcription Factors - genetics

Cilia - metabolism

Protein Transport - genetics

Cilia - genetics

Transcription Factors - metabolism

Animals

Smoothened Receptor

HEK293 Cells

Bardet-Biedl Syndrome - genetics

Mice

Receptors, G-Protein-Coupled - genetics

RNA, Small Interfering - metabolism

Details

Title: Subtitle: A novel protein LZTFL1 regulates ciliary trafficking of the BBSome and Smoothened
Creators: Seongjin Seo - Department of Pediatrics, University of Iowa College of Medicine, Iowa City, Iowa, USA
Qihong Zhang
Kevin Bugge
David K Breslow
Charles C Searby
Maxence V Nachury
Val C Sheffield
Resource Type: Journal article
Publication Details: PLoS genetics, Vol.7(11), e1002358
DOI: 10.1371/journal.pgen.1002358
PMID: 22072986
PMCID: PMC3207910
NLM abbreviation: PLoS Genet
ISSN: 1553-7390
eISSN: 1553-7404
Publisher: United States
Grant note: REY110298 / PHS HHS\r\nR01GM089933 / NIGMS NIH HHS\r\nHoward Hughes Medical Institute\r\nR01 GM089933 / NIGMS NIH HHS\r\nREY017168 / PHS HHS\r\nR01 EY017168 / NEI NIH HHS
Language: English
Date published: 11/2011
Academic Unit: Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
Record Identifier: 9983980079402771

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