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Lkb1 interacts with a ciliopathy complex to regulate inflammation

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Canis lupus familiaris

PROVIDER: GSE86011 | GEO | 2018/06/10

REPOSITORIES: GEO

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Lkb1 interacts with a ciliopathy complex to regulate inflammation (array)

Project description:Ciliopathies comprise a spectrum of inherited disorders involving different organ systems such as the central nervous system, the skeleton, and the kidney1. The cilium is a hair-like organelle at the cell surface that acts as a sensor and signal transducer2. Many ciliopathy manifestations can be linked to deficient cilia function, yet it is unclear how a cilium defect results in nephronophthisis (NPHP), the most prevalent renal manifestation in children, characterized by inflammation, interstitial fibrosis, and renal cysts3. Here, we report that deletion of the serine threonine kinase Lkb1 in the mouse kidney results in cardinal features of nephronophthisis. An in-vivo proteomic interaction screen revealed ANKS3, a known interaction partner of the nephronophthisis protein NPHP1, and its interactor NEK7 as novel binding partners of LKB1. Lkb1 genetically interacts with Nphp1 in zebrafish. Unbiased transcriptional analysis in-vitro and in-vivo revealed that the chemokine CCL2 is upregulated in Lkb1 deficiency and is accompanied by recruitment of CCR2 expressing mononuclear cells in the kidney. CCL2 regulation requires NPHP1, ANKS3 and NEK7. These findings link LKB1 and ciliopathy proteins to immune regulation and explain how mutations in NPHP proteins result in fibrosis of the kidney.

2018-06-10 | GSE86009 | GEO

Lkb1 interacts with a ciliopathy complex to regulate inflammation (RNA-Seq)

2018-06-10 | GSE86010 | GEO

Lkb1 interacts with a ciliopathy complex to regulate inflammation

Project description:Lkb1 interacts with a ciliopathy complex to regulate inflammation

| PRJNA339988 | ENA

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